bluuebunny/crossref_metadata_2025 huggingface dataset:
H‐2‐unrestricted polyclonal maturation without replication of small B cells induced by antigen‐activated T cell help factors
Authors: Melchers Fritz , Andersson Jan , Lernhardt Waldemar , Schreier Max H.
Published: February 2007

Lines and clones of helper T cells, specific for either horse or sheep erythrocytes, when brought together with specific antigen and I region‐histocompatible macrophages, release factors which stimulate B cells to replicate and mature to Ig secretion (BRMF).

BRMF act differently on activated B cells and on resting, small B cells. B cell blasts, activated by either lipopolysaccharide (LPS) or by lipoprotein, as well as “background” B cell blasts of normal spleen, are restimulated by BRMF to continued replication and maturation to Ig secretion. Between 10 and 50% of the activated B blasts from spleens of a variety of mouse strains, either I region‐compatible or not, are stimulated. BRMF, therefore, act as B cell mitogens, stimulating activated B blasts to rounds of division and maturation to Ig secretion in the absence of specific antigen, irrespective of the H‐2 haplotype of the B blasts.

Resting, small B cells, on the other hand, are not stimulated to replication by the same preparations of BRMF, even in the presence of specific antigen. However, within one day, large, blast‐like cells appear in culture. These blast‐like cells do not incorporate thymidine, do not divide, but mature to secretion of IgM and IgG. Within 4 to 5 days of stimulation by BRMF, about one‐third of all splenic B cells develop in this way, and 10–20% of them secrete sufficient amounts of Ig to form hemolytic plaques. Furthermore, activation of small, resting splenic B cells is H‐2‐unrestricted and polyclonal. The nonreplicating blast‐like cells lose their capacity to replicate as they mature to Ig secretion. This capacity, on stimulation with either LPS or with antigen‐activated T cell help, is reduced by 90–93% to 99.7% within 1–2 days. This loss of capacity to replicate is discussed in view of models for tolerance induction which imply clonal elimination by terminal maturation.
Selection of bacterial mutants from Salmonella specifically recognizing determinants on the cell surface of activated T lymphocytes A novel system to define cell surface structures
Authors: Lehmann Volker , Streck Helmut , Minner Inge , Krammer Peter H. , Ruschmann Ellen
Published: February 2007

The isolation of bacterial mutants from Salmonella is described with specific binding capacities to allogeneically or concanavalin A‐activated T lymphocytes. The enrichment of these mutants was achieved by separation of T cell blasts with adhering mutants from nonresponsive lymphocytes and nonadhering bacteria through 1 × g sedimentation. Binding of the mutants was specific for T cells early after antigen or mitogen stimulation. No adherence was observed with unstimulated T or B lymphocytes and with B cell blasts. Further results suggested that the binding of Salmonella mutants was mediated by the heteropolysaccharide moiety of lipopolysaccharides with a specificity for protein receptor sites on activated T lymphocytes. Significantly, these heteropolysaccharides also inhibited the differentiation of prekiller to killer cells from allogeneic mixed lymphocyte cultures but did not depress the proliferative response or the activity of cytotoxic effector cells. Bacterial adherence, as well as polysaccharide activity in functional tests, showed strain specificity since reactivity could only be obtained with activated T cells from AKR, C 57 BL/6, C 3 H but not with BALB/c and A/J strain mice. It is discussed whether the heteropolysaccharides mimic the structure of naturally occurring molecules and thus compete for their receptor sites. Selection of bacterial mutants with adherence properties may become a general procedure for detecting cell surface molecules on lymphoid and nonlymphoid cells.
A monoclonal antibody blocking human T cell function
Authors: Reinherz Ellis L. , Hussey Rebecca E. , Schlossman Stuart F.
Published: February 2007

The possible functional role of T cell surface antigens defined by monoclonal antibodies was investigated. Five monoclonal anti‐T cell reagents as well as an anti‐la and anti‐β2‐microglobulin antibody were examined for their effect on T cell function. It was shown that an antibody termed anti‐T3, reactive with all peripheral T cells, blocked T cell proliferative responses to soluble and cell surface antigens. This inhibition was seen when T lymphocytes were treated with as few as 104 anti‐T 3 molecules per cell. Although anti‐T 3 could block the generation of cytotoxic T cells in mixed lymphocyte culture, once generated, anti‐T3 had no effect on cytotoxicity. In addition, anti‐T 3 abrogated the ability of T cells to provide help to B cells in a pokeweed mitogen‐driven immunoglobulin system. More importantly, these functional effects were not seen with the other monoclonal antibodies. Both the appearance of this antigen in intrathymic ontogeny and its critical role in T cell function suggests that the T3 molecule is related to an important antigen recognition receptor or cell‐cell interaction molecule.
Immunopathology of chickens infected in vivo and at hatching with the avian osteopetrosis virus MAV.2–0
Authors: Hirota Yoshikazu , Martin Maria‐Teresa , Viljanen Matti , Toivanen Paavo , Franklin Richard M.
Published: February 2007

The immunological capacity of chickens infected with MAV.2–0, an avian osteopetrosis virus, was studied both morphologically and functionally. Infection of 11 to 12‐day‐old embryos with a high (0.58 × 106‐1.2 × 106 plaque‐forming units; PFU) and an intermediate (5.8 × 104 PFU) dose of virus resulted in severe stunting, as manifested by lower body and lymphoid organs (bursa, thymus and spleen) weights. The bursa and spleen of osteopetrotic chickens were poorly developed, the thymus partially necrotized; all lymphoid organs had fewer lymphocytes than controls, and there were far fewer germinal centers in the spleen of infected birds, as compared to controls. The humoral and cellular immunity of these osteopetrotic chickens was significantly suppressed, as assessed by (a) the plaque‐forming cell response against sheep red blood cells (SRBC) in the spleen; (b) circulating antibody responses against SRBC, Brucella abortus and human γ‐globulins (HGG); (c) the delayed hypersen‐sitivity reaction against HGG; and (d) mitogenic responsiveness of peripheral blood and spleen lymphocytes to concanavalin A, phytohemagglutinin M and pokeweed mitogen. A few birds, infected as 11‐day embryos with the lowest concentration of virus (2.9 × 104 PFU) had no palpable bone lesions, the lymphoid organs had normal histology, and immune responses were quite similar to those in uninfected control birds. Osteopetrotic chickens, infected within 48 h after hatching (5.8 × 105 PFU), had normal IgM‐class antibody responses against all antigens studied (SRBC, Brucella, HGG), whereas IgG and/or IgA responses tended to be lower than those observed in the normal controls. These findings, together with the regularly organized small lymphoid follicles in the bursa, indicate a late affection of B cell development, whereas in the birds infected at 11–12 days of incubation, an almost total arrest of B cell development was observed. T cell functions of birds infected at hatching were suppressed to the same extent as those of in ovo infected birds indicating susceptibility of the T cell lineage to MAV.2–0 also at later stages of development.
Characterization of T cell surface glycoproteins T1 and T3 present on all human peripheral T lymphocytes and functionally mature thymocytes
Authors: van Agthoven Andre , Terhorst Cox , Reinherz Ellis , Schlossman Stuart
Published: February 2007

The monoclonal antibodies, anti‐T1 and anti‐T3, both react with all human peripheral thymus‐derived lymphocytes and with 10% of thymocytes; each, however, recognizes different cell surface structures. It was determined that the target antigen of anti‐T1 is a 69000 molecular weight cell surface glycoprotein and that the T3 antigen is a 19000 mol. wt. glycoprotein.
Studies on the nature and cellular distribution of TLMA — a major rat T axis differentiation antigen Identification as the glycosphingolipid GgOse4Cer (asialo GM1)
Authors: Arndt Rüdiger , Thiele Heinz‐Günter , Hamann Alf , Gräning Gisela , Raedler Andreas , Momoi Takashi , Wiegandt Herbert
Published: February 2007

The recently detected T axis differentiation antigen, which was provisionally designated as T‐lymphocyte‐macrophage‐associated antigen (TLMA) could now be identified as the neutral glycosphingolipid GgOse4Cer (asialo‐GM1).

TLMA is not only expressed on lymphocytes on the T lineage and on macrophages of the rat, but also on eosinophilic cells. On erythrocytes, the determinants are only detectable after neuraminidase treatment.

Within the cell surface of thymic lymphocytes, the antigen determinant is partly masked by sialic acid residues. Presently, it cannot be decided whether the masking effect is brought about by sialic acid residues of adjacent glycolipid molecules or whether a nonreactive sialylated precursor molecule exists.
Enhancing effect of murine anti‐idiotypic serum on the proliferative response specific for poly(LTyr, LGlu)‐poly(DLAla)–poly (LLys) [(T, G)‐A–L]
Authors: Lifshitz Ruth , Parhami Behnaz , Mozes Edna
Published: February 2007

Murine anti‐idiotypic serum against C3H.SW anti‐poly(LTyr, LGlu)‐poly(DLAla)–poly(LLys) [(T, G)‐A–L] antibodies was elicited in C57BL/6 mice. The effect of the anti‐idiotypes on the proliferation of primed lymph node cells was investigated. The anti‐idiotypic serum stimulated the proliferative response of the (T, G)‐A–L‐specific lymph node cells as well as of nylon wool‐enriched T cells. In the presence of suboptimal doses of (T, G)‐A–L, the addition of the anti‐idiotypes enhanced the proliferation to the levels obtained with the optimal dose of (T, G)‐A–L itself. These results suggest the existence of shared idiotypic determinants between antibodies and the (T, G)‐A–L‐specific proliferative T cells.
Ontogeny of B lymphocyte function X. Strain differences in maturation of the capacity of the B lymphocyte population to produce a high‐affinity antibody response
Authors: Sherr David H. , Francus Tova , Szewczuk Myron R. , Kim Young T. , Sogn Dorothy , Siskind Gregory W.
Published: February 2007

The ontogeny of the B lymphocyte population to be capable of producing a high‐affinity plaque‐forming cell (PFC) response to a haptenic determinant was studied by cell‐transfer techniques in five different mouse strains. Lethally irradiated adult mice were reconstituted with liver from fetal or neonatal donors or spleen from young donors as a source of B lymphocytes. In addition, all animals received 1 × 108 adult thymus cells. Recipients were immunized with dinitrophenylated bovine gamma‐globulin (DNP‐BGG) one day after cell transfer. The heterogeneity of affinity of their anti‐DNP PFC response was assayed by hapten inhibition of plaque formation. It was established by use of congenic mice differing at the Igh locus that only donor cells responded under these conditions. By use of this transfer system, it was shown that the B cell populations of A/HeJ, AKR and C57L/J mice aquire the capacity to produce a high‐affinity PFC response between day 15 and 18 of fetal life. The B cell populations of LAF1 and DBA/1 J mice mature between 7 and 10 days after birth. The B cell population of C57BL/6 J mice matures between 21 and 28 days of age. In LAF1 and AKR mice, the B cell population acquires the capacity to generate a high‐affinity indirect PFC response at approximately the same time as the capacity to generate a high‐affinity direct PFC response. The time of maturation of the capacity to generate indirect PFC was found to differ in different strains of mice. Maturation of the capacity to produce indirect PFC appears to represent a dinstinctly different differentiation event from the acquisition of the capacity to produce a high‐affinity PFC response. The data suggest that the maturation of the B cell population to be capable of producing high‐affinity PFC is a precisely regulated differentiation event, the timing of which is strain‐related. Preliminary data suggest that this regulation is not linked to either the H‐2 haplotype or to the Igh allotype.
T cell‐mediated immunity to oncornavirus‐induced tumors IV. Preliminary evidence for a specific suppression of anti‐Moloney cell‐mediated immune response by autoimmune T cells
Authors: Leclerc Jean‐Claude , Plater Christine , Connan Francine , Debré Patrice
Published: February 2007

Previous reports have demonstrated that adult C 57 BL/6 mice infected with murine sarcoma virus (MSV) develop a strong cell‐mediated immune response against Friend, Moloney, Rauscher virus‐induced type‐specific (FMR) antigens and reject their tumors. To demonstrate a possible role for auto‐anti‐MSV T blasts, syngeneic C 57 BL/6 mice were immunized with highly enriched anti‐FMR cytolytic T cells. One of 3 pools of these autoimmune T cells prepared from 12 surviving immunized mice (a) inhibited specifically the in vitro anti‐MSV cytolysis generation and (b) enhanced drastically the MSV tumor growth in vivo. The possibility for such an immunization procedure to induce anti‐idiotype T cells, the repeatability of this effect and the relationship of the suppressor cells with antigen‐specific suppressor cells and other components of the anti‐MSV immune response are discussed.
Fine specificity mapping of two allospecific T cell lines: recognition of private specificities in the H‐2 IA subregion
Authors: Dennert Gunther , Swain Susan L. , Waterfield J. Douglas , Warner John F. , Dutton Richard W.
Published: February 2007

Two allospecific T cell lines, C.C3.11.75 (H‐2d anti‐H‐2k) and B6.C.7.76 (H‐2b anti‐H‐2d), established from mixed lymphocyte cultures, were selected by continuous antigenic stimulation over several years. Both cell lines proliferated to alloantigen, provided allohelp to B cells in the humoral antibody response, and one of them showed cytolytic activity. Using spleen cells from various congenic mouse strains, the specificity of antigen recognition was examined in order to examine whether there is a correlation between T cell function and antigen recognition. Results showed that in all functional assays, the same antigenic determinant, a private specificity encoded in IA, was recognized. This shows that there is no obligatory correlation between T cell function and antigen recognition and may suggest that the T cell receptor repertoire is biased towards recognizing private specificities.
Interleukin 2, production in the syngeneic mixed lymphocyte reaction
Authors: Lattime Edmund C. , Gillis Steven , David Chella , Stutman Osias
Published: February 2007

In the syngeneic mixed lymphocyte reaction, Ly 1 cells proliferate following stimulation with Ia‐positive macrophage‐like cells. The proliferation is accompanied by the release of interleukin 2 into the medium. Both the proliferation and interleukin 2 production are dependent on the expression of Ia antigenic determinants, as the addition of haplotype‐specific anti‐Ia antisera to the cultures inhibits both parameters.
Interferon‐induced enhancement of macrophage‐mediated tumor cytolysis and its difference from activation by lymphokines
Authors: Boraschi Diana , Tagliabue Aldo
Published: February 2007

Mouse peritoneal macrophages expressed increased cytolytic activity against tumor cells upon in vitro exposure to partially purified L cell interferon (IFN‐β). In contrast, treatment with human IFN or with mock IFN preparations did not enhance macrophage tumoricidal capacity. Macrophage activation by IFN was optimal with long exposure times and high IFN concentrations. Treatment with polymyxin B sulfate did not affect IFN‐induced macrophage cytotoxicity, thus excluding the possibility that bacterial lipopolysaccharide contaminants were responsible for macrophage activation. Conversely, treatment with a highly specific anti‐IFN antiserum completely abolished IFN effect on macrophages, but had no effect on lymphokine‐induced cytolysis. IFN and the lymphokine macrophage‐activating factor (MAF) were compared for their ability to provide the sequence of activation signals to macrophages from the normal responder C3H/HeN mice and from C3H/HeJ mice, which are defective for several macrophage responses. Like MAF, IFN was incapable of inducing tumoricidal activity in C3H/HeJ macrophages. However, whereas MAF provided the first “priming” signal to macrophages of both strains, IFN acted as first signal only for C3H/HeN macrophages, being inactive for cells of the defective C3H/HeJ strain. Fürthermore, IFN was not capable of providing the second “expression” signal to “primed” macrophages.

These data suggest two different macrophage activation pathways for IFN and MAF.
Malignant cells isolated from Burkitt's lymphoma but not other forms of leukemia activate the alternative complement pathway in human serum
Authors: McConnell Ian , Klein George , Macanovic Momir , Gorman Neil T. , Raniwalla Joher
Published: February 2007

Cells isolated directly from primary biopsies of Burkitt's lymphoma were found to activate the alternative complement pathway in hypogammaglobulinemic human serum. In contrast, cells isolated from patients with either acute lymphoblastic leukemia, chronic lymphocytic leukemia or chronic myeloid leukemia did not activate. No defects in the ability of Burkitt's lymphoma sera to support alternative pathway activation were detected.
Partial maturation and light chain restriction of Abelson virus‐transformed B cell precursors
Authors: Boss Michael A. , Greaves Melvyn F. , Teich Natalie
Published: February 2007

The induction of partial maturation in an in vitro derived Abelson virus‐transformed murine lymphoid cell subline (ABC‐1/AT1) is described. Pre‐B (cytoplasmic, μ chain‐positive) lymphocytes were induced from presumptive B cell precursors by prostaglandin E1, butyric acid, lipopolysaccharide and interferon. Maturation was independent of alterations in cellular growth rate and could be achieved in the absence of cell division.

The AT1 subline was found to be restricted to the expression of a single light chain type (lambda) indicating a possible B cell lineage‐committed precursor as the target for viral transformation.
Immune unresponsiveness of spleen cells from lipopolysaccharide‐treated mice to particulate thymus‐dependent antigen I. Evidence for differentiation signal defect
Authors: Portnoï Denis , Motta Iris , Truffa‐Bachi Paolo
Published: February 2007

The cellular basis of the immune unresponsiveness induced by lipopolysaccharide (LPS) was analyzed at the B and T cell level. The immunosuppressive effect of LPS is not related to altered B cell competence. Inhibition of antibody responses was observed only for thymus‐dependent (TD) and not for thymus‐independent antigens. In the presence of T cell‐replacing factor (TRF), LPS‐sensitized B lymphocytes respond to TD antigenic stimulation and differentiate into antibody‐forming cells. Evidence is presented for a decreased helper activity of LPS‐sensitized T lymphocytes and for a defective production of TRF in concanavalin A‐stimulated spleen cells from LPS‐treated mice. The implication of a cell compartment other than T is discussed.
Surface antigens specifically expressed by activated T cells in humans
Authors: Corte Giorgio , Moretta Lorenzo , Damiani Guido , Mingari Maria C. , Bargellesi Antonio
Published: February 2007

By immunizing BALB/c mice with human T cells derived from a secondary mixed lymphocyte reaction (MLR) and successive fusion of the spleen cells with P3X63Ag8U1 myeloma cells, several monoclonal antibodies to activated T cells were obtained. Four of them (MLR 1‐4) were shown to be specific for activated T cells only, showing no reactivity with peripheral blood cells. The antigens recognized by these antibodies are differently distributed and appear on T cells at different times after stimulation. Thus, MLR 2 stains nearly all the responder T cells present in a secondary MLR, while MLR 1, 3 and 4 stain only a fraction. MLR 2 and 3 are also present on mitogen‐stimulated cells. At least 3 of these MLR antigens may define different sets of activated T cells, and are likely to become useful in monitoring T cell activation also in the course of diseases involving the immune system.
Terminal differentiation of T cells specific for mutant H‐2K antigens. Conversion of Lyt‐1,2 cells into Lyt‐2 but not Lyt‐1 cells, in vitro
Authors: Nagy Zoltan A. , Kusnierczyk Piotr , Klein Jan
Published: February 2007

The Lyt phenotype of T cells at different stages of response to mutant H‐2K antigens was determined by immunofluorescence using monoclonal rat anti‐Lyt antibodies. Previous observations indicated a differential expression of the two allelic forms of Lyt‐1 antigen on these cells. Since the rat antibodies recognize nonpolymorphic framework determinants of Lyt antigens, in our approach the expression of both Lyt‐1 alleles was analyzed with the same antibody. It was found that cells reacting to three different H‐2K mutants have the Lyt‐1,2 phenotype, regardless of the Lyt‐1 allele carried by the responder strain. The Lyt phenotype of responder cells remained unchanged after priming in vivo. However, cells recovered from cultures after secondary stimulation in vitro were mainly Lyt‐2, with few Lyt‐1,2 and virtually no Lyt‐1 cells present. This change of Lyt phenotype ran in parallel with the loss of proliferative capacity to the priming antigen, but cytolytic activity of the cells remained unimpaired. Long‐term proliferation of T cells induced against mutant H‐2K antigens could only be maintained in the presence of a T cell growth factor. Cultures with growth factor contained almost exclusively Lyt‐2 cells and exerted strong cytolytic activity. These results demonstrate that the Lyt differentiation pathway of anti‐mutant T cells is from Lyt‐1,2 to Lyt‐2. Furthermore, the data suggest that no helper cells are induced in response to mutant H‐2K antigens. A model which incorporates these findings into current concepts of T cell differentiation is discussed.
Cytotoxic T cell response against lymphoblasts infected with Moloney (Abelson) murine leukemia virus. Methodological aspects and H‐2 requirements
Authors: Stukart Marijke J. , Vos Annemieke , Melief Cornelis J. M.
Published: February 2007

A method for infection of lymphocytes with Moloney(Abelson) murine leukemia virus [M(A)‐MuLV] is described. Only lymphoblasts obtained after stimulation of normal spleen cells by the B cell mitogen lipopolysaccharide (LPS) were satisfactory targets for virus‐specific, secondary cytotoxic T lymphocytes (CTL), whereas spleen cells stimulated by the T cell mitogen concanavalin A were not. The secondary CTL response against M(A)‐MuLV could be efficiently measured using M(A)‐MulV‐infected LPS blasts as stimulating cells for secondary in vitro restimulation and as target cells for virus‐specific destruction. Cold target inhibition demonstrated virus specificity of CTL. The T cell character of the cytotoxic cells was demonstrated by their sensitivity to anti‐Thy‐1.2 treatment. Using syngeneic virus‐infected LPS blasts as target and stimulator, CTL responses were measured with effector cells from C57BL mice of the H‐2b haplotype and of recombinant haplotypes sharing either K or D alleles with H‐2b. In analogy with previous studies on Moloney virus‐specific CTL. it was observed that C57BL/6 (H‐2b) effector cells predominantly lysed Db‐compatible, virus‐infected target cells; B10.A(5R), (KbDd) effector cells showed a poor CTL response against syngeneic, virus‐infected target cells. The combined findings indicate the existence of an Ir gene in the H‐2D region regulating the CTL response against Moloney leukemia virus.
Selected populations of alloreactive T cells contain helper T cells but lack ThId, an antigen‐specific helper T cell required for dominant production of the T15 idiotype
Authors: Bottomly Kim , Janeway Jr. Charles A.
Published: February 2007

Isolated, alloreactive T cell populations were primed with protein carriers in vivo and tested for their ability to provide help for an anti‐phosphorylcholine (PC) antibody response and for production of the T15 idiotype. It was found that alloreactive T cell populations would support anti‐PC antibody responses but did not selectively activate B cells capable of producing the T15 idiotype that normally dominates such responses. This failure to help for the production of the T15 idiotype was shown to be due to the absence of an antigen‐specific helper T cell that is required for dominant idiotype production (ThId). These studies suggest that ThId cells have recognition structures for antigen and for self idiotype, but lack recognition structures for major histocompatibility complex‐encoded antigens.
Functional and binding activity of monoclonal anti‐Thy‐1 antibodies: evidence for different expression of the two alleles
Authors: Abehsira Orly , Edwards Andrew , Simpson Elizabeth
Published: February 2007

Monoclonal anti‐Thy‐1.1 and anti‐Thy‐1.2 antisera selected for complement‐dependent cytotoxicity have high cytotoxic and binding titers on thymocytes and peripheral T cells of mouse strains bearing the appropriate Thy‐1 allele. The effect of both anti‐Thy‐1.1 and anti‐Thy‐1.2 monoclonal antisera plus complement on cytotoxic T cell effectors is to abrogate their activity. On the functional activity of precursor cytotoxic T cells, monoclonal antisera against the two alleles have different effects: anti‐Thy‐1.2 plus complement removes precursor activity of Thy‐1.2‐bearing strains, including (Thy‐1.1 × Thy‐1.2)F1 heterozygotes. In contrast, six different anti‐Thy‐1.1 monoclonals, including four of the IgM class and two of the IgG class, failed to remove cytotoxic precursor activity from the splenic T cells of AKR, A. Thy‐1.1 or (CBA × AKR)F1 mice. Analysis by fluorescence‐activated cell sorting of in vitro cultured AKR spleen cells shows that Thy‐1.1 antigen appears on the cell surface during the five‐day culture period.
DNL 1.9: a monoclonal antibody which specifically detects all murine B lineage cells
Authors: Dessner Deborah S. , Loken Michael R.
Published: February 2007

A rat anti‐mouse monoclonal antibody, DNL 1.9, has been produced and shown to bind to all cells of the B lineage in mice. By quantitative immunofluorescence, DNL 1.9 binds to approximately 50% of spleen cells, 20–30% of lymph node cells, but not to thymocytes. In bone marrow and neonatal liver, 70–80% of the small cells and 10–20% of the large cells were identified by this antibody. Two‐color immunofluorescence studies showed that all immunoglobulin‐positive cells were also DNL 1.9‐positive, while Thy‐1.2‐positive cells did not bind the monoclonal antibody. All pre‐B cells in bone marrow, as identified by cytoplasmic IgM staining, were labeled by the DNL 1.9 antibody. A significant proportion of lymphocytes in the bone marrow which did not express cell surface immunoglobulin did bind DNL 1.9. Both direct and indirect plaque‐forming cells were also shown to bind DNL 1.9 antibody. The antigen recognized by this monoclonal antibody was not immunoglobulin nor was the antigen present in normal mouse serum. All seven mouse strains tested showed similar patterns of antigen expression. These results show that all of the cells identifiable as being of the B lineage were identified by this monoclonal antibody. It is possible that the cells which bind DNL 1.9 but do not express cell surface immunoglobulin may be very early precursors of B lymphocytes.
Requirement of the immunogen (E. coli β‐galactosidase) for the response towards a determinant responsible for antibody‐mediated enzyme activation, while antibodies binding some other sites can be elicited by mitogen alone
Authors: Piccolella Enza , Centis Dora , Celada Franco
Published: February 2007

Virgin mouse spleen cells cultured in vitro without antigen or mitogen produce a measurable amount of IgM binding E. coli β‐galactosidase (β‐gal). Lipopolysaccharide (LPS) and LPS plus antigen enhance this response, which cannot be considered truly polyclonal since it does not include the production of antibodies directed towards a conformation‐dependent determinant, responsible for the activation of a mutant β‐gal, and known otherwise to be highly immunogenic. By priming in vivo with alum‐treated β‐gal (unable to elicit activating antibodies), an activating response is obtained in vitro by LPS plus antigen, but not by LPS alone.

These results are compatible with a two‐signal requirement for the activation of B cells and may be explained as follows: (a) the mitogen, in absence of immunogen, stimulates those clones which have a specific signal from cross‐reacting structures in the environment; (b) instead, no cross‐reactions are available for the conformation‐controlled structure of the „activating”︁ determinant; thus, intact immunogen is required as well as mitogen. Because of this „uniqueness”︁, the molecule of β‐gal offers a highly specific tool to probe carrier‐hapten relationships in native proteins.
Lymphocyte transformation induced by autologous splenocytes incorporated with the tetrasialoganglioside GQ1b
Authors: Sela Ben‐ami
Published: February 2007

Incorporation of the tetrasialoganglioside GQ1b into membranes of mouse splenocytes rendered these cells effective triggers in an autologous mixed lymphocyte reaction. Whereas GQ1b‐incorporated cells increased mitogenic responses of thymocytes by 10 to 13‐fold over untreated cultures, the trisialoganglioside GT1b was only partially effective, and the di‐ and monosialogangliosides tested had no effect. The mixed lymphocyte reaction generated in the autologous system by highly glycosylated gangliosides is abolished by neuraminidase or mild formic acid treatmnt prior to their insertion into target cell membranes suggesting a role for the extra sialic acid residues in imparting additional antigenic specificity to the modified cells.
The distribution of Helix pomatia lectin receptors on mouse lymphoid cells and other tissues
Authors: Mattes M. Jules , Holden Howard T.
Published: February 2007

The distribution of receptors for the Helix pomatia lectin on mouse lymphoid cells and other tissues was investigated. Using a sensitive resetting assay combined with immunofluorescence, lectin receptors were found on the membrane of approximately 90% of peripheral T lymphocytes, 75% of thymocytes, 30% of bone marrow cells, 20% of nude spleen cells, 15–50% of peritoneal exudate macrophages, and a subpopulation of peritoneal exudate mast cells. The Thy‐1‐positive nude spleen cells were predominantly Helix lectin receptor‐negative. Approximately 5% of B lymphocytes were weakly positive, and neutrophils were negative. Receptors were present also on a subpopulation of cells of a fibroblast cell line and in acetone powder from the liver and, at a lower level, from the kidney and brain. Membrane receptors on all cell types were partially detectable without neuraminidase treatment of the cells. Two methods of fractionating Helix lextin‐positive cells were employed, which gave significantly different results. By rosetting and depletion using density fractionation, T cell mitogen responses were abolished, while B cell mitogen responses, T cell cytotoxicity, and natural killer cytotoxicity were only slightly affected, if at all. Helix lectinagarose column fractionation seemed more sensitive, in that essentially all natural killer cells bound to the column, as well as a considerable number of B lymphocytes. Cytotoxic T cells were heterogeneous: roughly half were not bound, but the remainder were bound and eluted.
Agents which block membrane lipid peroxidation enhance mouse spleen cell immune activities in vitro: relationship to the enhancing activity of 2‐mercaptoethanol
Authors: Hoffeld J. Terrell
Published: February 2007

A broad spectrum of agents known to block various steps in the lipid peroxidation process were tested for their ability to protect mouse spleen cells and thereby enhance their activities, in vitro, in either the primary antibody response or the lipopolysac‐charide‐stimulated proliferation response. Each agent (superoxide dismutase, butylated hydroxyanisole/butylated hydroxytoluene/n‐propyl gallate, lucigenin, and α‐tocopherol) was able to enhance the cellular response in both assay systems. The degree of enhancement of these immune functions was in proportion to the efficacy of each agent in blocking the overall process in lipid peroxidation. Previous work in this laboratory has shown that the enhancement of the primary antibody response by 2‐mercaptoethanol (2‐ME) is mediated by the enhanced availability of reduced glutathione in the culture medium. Suboptimal doses of each lipid antioxidant agent were able to enhance the antibody response in an additive manner with a suboptimal dose of 2‐ME up to a maximum response equal to that achieved with an optimal dose of 2‐ME alone. These data support the hypothesis that the enhancement of cellular responses in the presence of 2‐ME is mediated by the lipid antioxidant activity of reduced glutathione.
Immune suppression to nucleosides: differences between NZB and NZW mice
Authors: Young Michael C. , Bangs James D. , Borel Yves
Published: February 2007

Previous studies (Y. Borel and M. C. Young, Proc. Natl. Acad. Sci. USA 1980. 77: 1593) have shown that one can raise nucleic acid‐specific suppressor T cells which diminish either the T‐dependent immune response in vivo or the T‐independent immune response in vitro. The results presented here confirm and extend these observations in several different strains of mice. Administration of nucleoside‐modified spleen cells diminishes antibody‐forming cells to nucleoside in mice immunized with nucleoside linked to keyhole limpet hemocyanin (KLH). Immune suppression was obtained in all strains except SJL and NZW, which are known to be high responders to denatured DNA. Both the primary and secondary immune responses were suppressed in C57BL/6 mice. Autologous cells exhibit a different ability to function as carriers. Spleen cells are the most effective, and to a certain extent, thymus cells. In contrast, bone marrow cells and red cells fail to induce immune suppression.

A strain difference was found between NZB and NZW mice in their susceptibility to immunosuppression by nucleoside‐modified spleen cells. Whereas NZB mice are high responders to nucleoside‐KLH, they were easily suppressed by nucleoside coupled to spleen cells.

In contrast, NZW mice, although relatively low responders to nucleoside‐KLH, were not suppressed by administration of nucleoside coupled to spleen cells. Both male and female (NZB × NZW)F1 mice appeared to behave like the NZW parental strain and were resistant to immunosuppression by nucleoside‐modified spleen cells. The significance of this observation for the pathogenesis of murine systemic lupus erythematosus is discussed.
Demonstration of T15 idiotype‐positive effector and suppressor T cells for phosphorylcholine‐specific delayed‐type hypersensitivity response in CBA/N or (CBA/N X BALB/c)F1 male mice
Authors: Sugimura Kazuhisa , Kishimoto Tadamitsu , Maeda Keiji , Yamamura Yuichi
Published: February 2007

Subcutaneous immunization of CBA/N or (CBA/N x BALB/c)F1 (NBF1) male mice, which were defective in phosphorylcholine (PC)‐specific humoral antibody response, with PC‐conjugated syngeneic spleen cells induced a PC‐specific delayed‐type hypersensitivity (DTH) response, while intravenous administration of the same cells induced PC‐specific suppressor T cells for the DTH response. Treatment of PC‐specific effector or suppressor T cells for the DTH response induced in NBF1 male mice with anti‐T15 idiotypic antibody inactivated effector or suppressor functions of these T cells implying that PC‐specific T cells in NBF1 mice expressed T15 idiotypic determinants on their surface. Enrichment of PC‐specific suppressor T cells was also shown by employing anti‐T15 antibody‐coated dishes.
Characterization of immunological depression in spontaneously hypertensive rats
Authors: Takeichi Noritoshi , Suzuki Kazufumi , Kobayashi Hiroshi
Published: February 2007

Immunocompetent cell functions were evaluated in spontaneously hypertensive rats (SHR). Hematological studies revealed decreased absolute numbers of lymphocytes and increased numbers of polynucleic cells in the peripheral blood of SHR. The SHR had a reduced number of immature T lymphocytes in their thymuses in comparison with an original strain of Wistar rats, as detected by the rosette formation test with guinea pig erythrocytes. The antibody response to sheep red blood cells (SRBC) of the 3‐month‐old SHR was profoundly depressed and was about one‐tenth that of the Wistar rats. Cell cooperation experiments suggest that the T lymphocytes of the SHR were selectively impaired in antibody responses to SRBC in cooperation with B lymphocytes. B lymphocytes from the bone marrow of the SHR were not affected and produced normal numbers of plaque‐forming units. Cyclophosphamide treatment, which selectively depletes suppressor T lymphocytes, did not enhance the delayedtype hypersensitivity response to SRBC in SHR. This may rule out the possibility of the involvement of the suppressor mechanism in the T cell depression of the SHR.
Distribution of IgG and IgM receptors on human peripheral natural killer cells measured on the level of the single effector cell
Authors: Jondal Mikael , Merrill Jean E.
Published: February 2007

Using an agarose single‐cell cytotoxicity assay simultaneously with the antibodycoated ox erythrocyte assay for detecting Fc receptor (FcR)‐positive cells, the number of natural killer (NK) cells in fresh human peripheral blood which bear FcR for IgG or IgM have been determined. Of the target binding cells (TBC) which form conjugates with NK‐sensitive target cell lines Molt 4, 1301 and Hd‐Mar. 55% had FcR for IgG and 24% had FcR for IgM. In the active NK cell population, which amounts to about 6% in nylon wool column‐passed peripheral lymphocytes, cells with FcR for IgG account for 60% and cells with FcR for IgM for 17% of the total killing. Even though there is an increase in the number of FcR‐IgM‐positive cells from fresh peripheral blood after overnight incubation at 37°C, no increase was found in FcR‐IgM‐positive NK cells. The reasons why FcR for IgM have not been described earlier on human NK cells are discussed, as well as the functional implications of these and their probable expression on other types of cytotoxic effector cells.
Enhancement of monocyte thromboplastin activity by antigenically stimulated lymphocytes: a link between immune reactivity and blood coagulation
Authors: van Ginkel Cornelis J. W. , Zeijlemaker Willem P. , Stricker Liesbeth A. M. , Oh Johannes I. H. , van Aken Willem G.
Published: February 2007

Immune reactions are often associated with fibrin deposition. The mechanisms that lead to this fibrin formation have not yet been clarified.

In this study, we show that mononuclear leukocytes (MNL) from donors with a high proliferative response to protein derivative of tuberculin (PPD) have on average 2.5 to 15‐fold more thromboplastin (TP) activity, both exposed and intracellularly, compared with MNL from low responder after 4, 7 and 11 days of culture in the presence of PPD. This difference was not observed between the two groups of donors when PPD was omitted from the culture medium. Further evidence for a specific enhancement of the leukocyte TP activity can be derived from the about 4‐fold increase in TP activity of the bilateral mixed leukocyte culture relative to the individually cultured controls after 7 days of incubation.

TP activity was associated selectively with the monocytes in a PPD‐stimulated culture of MNL. The PPD‐specific enhancing effect on the leukocyte TP activity could be transferred by soluble factor(s) from stimulated lymphocytes to purified monocytes, which suggests that the effect is, at least partially, mediated by lymphokine(s).
Lymphoblastogenesis stimulates proliferation of interacting Lyt1 T cells in a syngeneic system
Authors: Reimann Jörg , Kaufmann Stefan H. E. , Diamantstein Tibor
Published: February 2007

The intravenous transfer of polyclonally activated lymphoblasts elicited a proliferative response of host‐derived Lyt1 T cells in the spleens of syngeneic recipient mice. These Lyt1 T cells (responding in vivo to a syngeneic lymphoblast graft) stimulated proliferation of resting, syngeneic splenic Lyt1 T cells, derived from uninjected mice, in a one‐way syngeneic mixed lymphocyte culture in vitro. The data are discussed in the context of T cell activation induced by lymphoblastogenesis in a syngeneic system.
Evidence for immediate hypersensitivity phenomena in experimental autoimmune uveoretinitis
Authors: de Kozak Yvonne , Sainte‐Laudy Jean , Benveniste Jacques , Faure Jean‐Pierre
Published: February 2007

Evidence is presented for the involvement of immediate hypersensitivity phenomena in experimental autoimmune uveoretinitis, an ocular inflammatory disease induced in Lewis rats by injection of the purified S antigen from bovine retina. Several parameters at various dates after immunization have been studied. In vivo degranulation of choroidal mast cells, in vitro degranulation of peritoneal mast cells in the presence of S antigen and cutaneous anaphylaxis were observed as early as 6–8 days after immunization. Serum antibodies were detected by passive hemagglutination from day 7 on. These phenomena preceded the onset of the ocular inflammation, consisting of a transient polymorphonuclear leukocyte infiltration, a long‐lasting lymphoid cell infiltration and extensive damage to the retina and surrounding tissues. Such time course of events may suggest a role for reaginic antibody as a trigger for vascular changes in the target ocular tissue, favoring the development of inflammatory lesions.
Transglutaminase as a marker for subsets of murine macrophages
Authors: Schroff Gotthard , Neumann Christine , Sorg Clemens
Published: February 2007

Transglutaminase was detected either at the single cell level by fluorescent staining with dansylcadaverine or in cell homogenates by incorporation of [14C] putrescine into α‐casein. In the mouse it was found that erythrocytes, granulocytes, thymocytes or lymphocytes with or without concanavalin A stimulation were negative in the fluorescence test. Normal peritoneal washout macrophages and peritoneal exudate cells stained positive to varying degrees (induced with mineral oil 64%, with thioglycollate 50%, with proteose peptone 22%, normal washout 1%). Macrophages from bone marrow liquid cultures were 20% positive at day 3 and 100% at day 17. Promonocytes and monocytes were negative. Positively stained cells also phagocytosed opsonized sheep erythrocytes. The degree of staining varied considerably in the macrophagelike cell lines IC21 (100%), J774.2 (75%), P388‐D1 (50%). This result and those from autoradiography studies indicate that expression of transglutaminase is not associated with the S‐phase of the cell cycle. The fluorescence test correlates quantitatively with the [14C] putrescine incorporation test. The enzyme is Ca2+‐dependent and appears neither to be on the outer cell surface nor being released into the culture medium. Circumstantial evidence indicates that it is also not compartmentalized in cytoplasmic vesicles. While the induction and modulation of enzyme expression is still under study, it is concluded that transglutaminase is a new marker for macrophages of a certain differentiation or activation state.
Lack of age‐associated auto‐anti‐idiotypic antibody regulation in mucosal‐associated lymph nodes
Authors: Szewczuk Myron R. , Campbell Rita J.
Published: February 2007

It has previously been shown that the loss of immune competence in the splenic B cell population with age may be due to auto‐anti‐idiotypic antibody regulation (M. R. Szewczuk and R. J. Campbell, Nature 1980. 286: 164). In the present study we have investigated the appearance of auto‐anti‐idiotypic antibody on immune B cells from the mucosal‐associated lymph nodes of old and young mice of the same strain. Various aged C57BL/6J male mice were immunized with 500 μg trinitrophenylated bovine gamma globulin (TNP‐BGG) in complete Freund's adjuvant (CFA) intraperitoneally. IgM, IgG and IgA anti‐TNP plaque‐forming cell (PFC) responses in the spleen, mediastinal and mesenteric lymph nodes were assayed for anti‐idiotype‐blocked, hapten‐augmentable PFC, 14 days later. It was found that 8 months or older C57BL/6J male mice produced a significantly high percentage of hapten‐augmentable IgM, IgG and IgA anti‐TNP PFC in the spleen. In contrast, there was a lack of hapten‐augmentable anti‐TNP PFC in the mesenteric and mediastinal lymph nodes with increasing age of the animal. Mice receiving antigen in the footpads and base of the tail also produced a significantly high percentage of hapten‐augmentable IgG PFC in the draining peripheral lymph nodes. TNP‐ε‐amino‐n‐caproic acid (EACA) as hapten was shown to specifically augment anti‐TNP PFC. Immune sera from 15‐month‐old mice caused a specific inhibition of anti‐TNP PFC in vitro. The inhibition of plaque formation was completely reversible by addition of TNP‐EACA as hapten. This PFC inhibitory activity in immune sera lacked anti‐TNP antibody activity, but reacted with anti‐TNP antibody of C57BL/6J origin. Immune sera from 8 month or older mice also revealed anti‐(anti‐TNP F(ab')2 IgG) titer as assayed by passive hemagglutination. Thus, the results of this study indicate a division of the immune system into regulatory compartments. Auto‐anti‐idiotypic antibody may be involved in a down‐regulation of systemic responses but with no apparent effect in the mucosal‐associated lymph nodes.
F4/80, a monoclonal antibody directed specifically against the mouse macrophage
Authors: Austyn Jonathan M. , Gordon Siamon
Published: February 2007

A hybridoma clone which secretes a macrophage (MΦ)‐specific monoclonal antibody, F4/80, was produced by fusing spleen cells from a rat hyperimmunized with cultured thioglycollate‐induced mouse peritoneal MΦ with a mouse myeloma, NS1. Binding of antibody to primary cells and cell lines was detected by radioimmune indirect binding assay, autoradiography or fluorescence‐activated cell sorter analysis. F4/80 binds to mouse MΦ from the peritoneal cavity or other sources, blood monocytes, MΦ derived from bone marrow precursors in culture and MΦ‐like cell lines, but not to other cells, including polymorphonuclear leukocytes, lymphocytes or fibroblasts. F4/80 does not bind to MΦ via Fc receptors, is not cytotoxic and is of the rat IgG2b subclass. Since F4/80 binds to all MΦ defined by adherence, morphology and immune phagocytosis, it provides a new marker to define the MΦ in the mouse. Large differences in expression of antigen F4/80 were found, depending on intraperitoneal stimulation, time in culture and stage of maturation. Immunoprecipitation experiments demonstrated that the antigen F4/80 is part of a component of Mr 160000 which is synthesized by the MΦ and, at least in part, exposed on the cell surface.
The killing of newborn larvae of Trichinella spiralis by eosinophil peroxidase in vitro
Authors: Buys Jannie , Wever Ron , van Stigt Rien , Ruitenberg E. Joost
Published: February 2007

Helminth infections in mammals are characterized by a high level of eosinophils in parasitized tissues and blood, and it has recently been suggested that these cells have a direct parasiticidal effect. Newborn larvae of Trichinella spiralis can be killed within 20 min by incubation at room temperature in a cell‐free system, including purified human eosinophil peroxidase (EPO), H2O2 and chloride at pH 5.5. Killing was measured by microscopic observation of the larvae. The larvicidal effect was dependent on each component of the EPO/H2O2/Cl− system and could be prevented by using SO42− instead of Cl−. Killing was totally inhibited by sodium azide and catalase, and substantially by bovine serum albumin, a protein that is an effective scavenger for HOCI. Since larvae could also be killed directly by HOCI under these conditions and EPO is able to oxidize Cl− to hypochlorous acid, it is very likely that the larvicidal effect of the EPO system is due to formation of hypochlorous acid. It is proposed that in vivo, the combination of EPO, which is exocytosed onto the surface of the parasite, and H2O2, which is generated by stimulated eosinophils, is responsible for the larvicidal effect.