bluuebunny/crossref_metadata_2025 huggingface dataset:
Allotype suppression in the chicken III. Analysis of the recovery from suppression by neonatally injected or maternal antibodies
Authors: Ratcliffe Michael J. H. , Ivanyi Juraj
Published: February 2007

Injection of M‐1 (Cμ), G‐1 (CμgM) heterozygous chickens on the day of hatch with anti‐IgM‐1 antiserum induced allotype suppression from which chickens recovered over a period of approximately 4 months. The suppression of the serum IgM‐1 levels was matched by a decrease in the number of splenic and peripheral blood B cells bearing the relevant IgM‐1 allotype, and a compensatory increase in the number of cells bearing the alternative nonsuppressed IgM‐1 allotype. However, the proportion of IgM‐1‐bearing bursal cells was only marginally altered. The recovery from suppression was due to B cell recruitment and could be abrogated by bursectomy. Allotype suppression induced in ovo or maintained by repeated injections of anti‐IgM‐1 anti‐serum resulted in chronic suppression and depletion of the relevant peripheral as well as bursal IgM‐1‐bearing cells. Antibody titers of the relevant allotype in partially suppressed chickens generally correlated with serum allotype levels without clonal restriction in antibody response of the suppressed allotype.
The peritoneal antigen‐presenting macrophage: control and immunogenic properties of distinct subpopulations
Authors: Tzehoval Esther , de Baetselier Patrick , Feldman Michael , Segal Shraga
Published: February 2007

The control of the immunogenic antigen‐presenting capacity of different subpopulations of thioglycollate‐induced peritoneal macrophages has been investigated. The experiments revealed the existence of two major subpopulations of macrophages, only one of which was highly efficient in educating antigen‐specific T cells. The other subpopulation, while highly phagocytic, was devoid of antigen‐presenting capacity. Further analysis, using specific antisera directed at H‐2I region gene products, revealed that the immunogenic antigen‐presenting population expressed H‐2I region‐controlled membrane antigens. Searching for cellular elements which control the differentiation of this antigen‐presenting macrophage subpopulation, it was found that its function was strictly controlled by T cells. T cell‐deficient mice (nu/nu) failed to generate a functional antigen‐presenting macrophage subpopulation. Transplantation of mature T lymphocytes to T cell‐deprived mice restored the immunogenic function of their antigen‐presenting macrophages. The results obtained suggest the existence of heterogeneity of functions among macrophage subpopulations and add a new regulatory function for T cells.
Primary and secondary in situ antibody response: abnormal affinity maturation pattern in mice carrying the xid gene
Authors: Huber Brigitte T. , Tokuhisa Takeshi , Herzenberg Leonore A.
Published: February 2007

The xid gene in mice controls a recessive defect resulting in the absence of a late maturing subset of B cells. Whereas the responsiveness pattern of these mice has been clearly defined in terms of their ability or inability to make antibodies to certain classes of thymus‐independent antigens, there are conflicting reports in regard to affinity maturation of the antibody response to thymus‐dependent antigens. To resolve this controversial issue, the two major isotypes of the IgG response, namely IgG1 and IgG2a were examined with a highly sensitive radioimmunoassay that measures both the magnitude and affinity of the anti‐2,4‐dinitrophenyl antibody of each isotype in individual serum samples. It was found that the xid gene reduced the amount but not affinity of the IgG1 antibody produced, whereas it impaired the whole IgG2a responses severely. In fact, mice carrying the defective gene were unable to mount a secondary IgG2a response, measured either quantitatively or qualitatively in terms of increased affinity. To test the possibility that Lyb3, an isogenic B celltriggering receptor lacking in xid‐mutant mice, plays a direct role in the maturation of the immune response, the antibody profile in normal mice immunized either with antigen alone or in combination with anti‐Lyb3 antiserum has been compared. It was found that triggering of the Lyb3 receptor substantially elevated and accelerated the primary IgG2a response, whereas it had little effect on the IgG1 response.
Induction and regulation of silent idiotype clones Idiotype regulation
Authors: Primi Daniele , Juy Dominique , Cazenave Pierre‐André
Published: February 2007

In order to study whether allotype linkage of idiotype expression is related to the total absence of structural gene(s) or to regulatory mechanisms acting on its phenotype expression, the M460 clone expression was followed in B cells from various inbred and recombinant strains of mice cultured at low density in the presence of lipopolysaccharide. Under these conditions, all cultures were found to contain anti‐trinitrophenyl (TNP) antibody plaque‐forming cells, some of which were inhibitable by anti‐M460 immunoglobulins.

In the course of these studies, it also became apparent that, even in the absence of T cells, B lymphocytes are able to exert regulatory functions. Experiments carried out using anti‐M460 hybrid cells F6 (51), and affinity‐purified anti‐(anti‐M460) antibodies revealed that clonotype regulation by B cells is mediated by idiotype‐auto‐anti‐idiotype interactions.
Human B lymphocytes form rosettes after insertion of T lymphocyte membrane constituents
Authors: Jakobovits Aya , Rosenberg Mireille , Sharon Nathan
Published: February 2007

Isolated plasma membranes from human thymocytes or peripheral T lymphocytes, upon their reconstitution with envelope glycoproteins of Sendai virus, afforded membrane vesicles that fused efficiently with human peripheral B cells. The B cells thus obtained acquired the ability to form regular rosettes at 4°C with sheep red blood cells. However, only B cells modified by fusion with thymocyte membranes formed stable rosettes at 37°C, a property which distinguishes thymocytes from peripheral T cells. Transfer of membrane components between human cells provides a new approach for the investigation of the sheep red blood cell receptor as well as the structure‐function relationship of other lymphocyte membrane components.
Anti‐Thy‐1‐mediated T cell activation. Role of soluble factors and expression of interleukin 2 receptors on T cells
Authors: Konaka Yoshiteru , Norcross Michael A. , Maino Vernon C. , Smith Richard T.
Published: February 2007

Rabbit anti‐Thy‐1 antibody bound to T cells induces the appearance of T cell growth factor (interleukin 2, IL 2) receptors and the production of IL 2. IL2 receptors induction by this means occurs within a short time span, and independent of any demonstrable accessory cell. A source of exogenous or endogenous IL 2 is apparently the only requirement for proliferation after these receptors are expressed. IL 2 production, on the other hand, is accessory cell‐dependent, and this help is mediated via Fc receptors on the accessory cell. IL 2 production in this model is demonstrable at 4–6 h, or earlier, and is proliferation‐independent. X‐irradiation actually augments apparent IL 2 production. The data are consistent with the hypothesis that a differentiated subset of T cells in any mixed population is responsible for IL 2 production.
Genetic control of the immune response to staphylococcal nuclease XI. Effects of in vivo administration of anti‐idiotypic antibodies
Authors: Sachs David H. , El‐Gamil Mona , Miller Geraldine
Published: February 2007

The effects of prior treatment with heterologous anti‐idiotypic antibodies on the response to staphylococcal nuclease (Nase) have been examined. Previous studies have shown that 100% of A/J mice treated with Nase in complete Freund's adjuvant produce anti‐Nase antibodies possessing a characteristic idiotype (Id). Mice treated with anti‐Id antibodies followed by Nase produced levels of Id equal to or greater than those of control animals treated with Nase alone. The appearance of Id in treated mice preceded the appearance of anti‐Nase activity, and animals treated with anti‐Id alone produced high levels of Id without detectable anti‐Nase activity. Id expression in such animals could be detected using anti‐Id reagents produced in several different species suggesting that it represented true idiotope expression rather than unrelated molecules reactive only with the anti‐Id reagent used for initial treatment. Isolation of the nonantigen‐binding Id‐bearing molecules (Id') showed them to be immunoglobulins bearing the same idiotopes as do anti‐Nase antibodies. However, quantitative comparisons of Id levels vs. amount of Id or Id'‐bearing immunoglobulin suggested that the nonantigen‐binding immunoglobulins bore fewer idiotopes per molecule than did anti‐Nase antibodies. Evidence was also obtained for the production of some nonantigen‐binding Id‐bearing molecules during the normal immune response Nase. These findings are therefore consistent with the existence of a network of Id‐anti‐Id interactions in the immune response to Nase.
Antibody feedback regulation in vitro: T helper cell activation and T‐B cell cooperation are not impaired by anti‐carrier antibody
Authors: Zubler Rudolf H.
Published: February 2007

Effects of antibody feedback regulation on T helper (Th) cell functions required in plaque‐forming cell (PFC) responses were studied in vitro. Using a sensitive functional assay, it was found that serum from immunized mice did not inhibit sheep erythrocyte (SRBC)‐, or keyhole limpet hemocyanin‐specific Th cell activation. SRBC‐“pulsed” splenic adherent cells activated Th cells more efficiently when pulsed in the presence of anti‐SRBC antiserum. PFC responses against 2,4,6‐trinitrophenyl (TNP) coupled to soluble carriers were studied under conditions in which linkage between hapten and the priming carrier was either required or not. Under both conditions, anti‐carrier antiserum had an enhancing or no effect; only anti‐hapten antiserum or monoclonal anti‐hapten antibody were inhibitory. Thus, these results did show that antibody feedback was essentially hapten‐specific and did not interfere with Th cell functions, except, possibly, that anti‐hapten antibody interfered with linked cooperation at the level of hapten‐B cell interaction, in addition to its inhibitory effect detectable under conditions of unlinked cooperation. Since SRBC‐pulsed, adherent cells were very inefficient in stimulating anti‐SRBC PFC responses, the results further suggested that phagocytosed antigen could only by recognized by Th cells but not by B cells. Finally, by attempting to further study hapten‐B cell interactions, no PFC responses against TNP coupled to soluble carriers could be generated by substituting for Th cells with different types of secondary mixed leukocyte culture supernatant in cultures with pure surface Ig‐positive cells. Only anti‐SRBC PFC responses were generated in such cultures.
Purification of Thy‐1‐related glycoproteins from human brain and fibroblasts: comparisons between these molecules and murine glycoproteins carrying Thy‐1.1 and Thy‐1.2 antigens
Authors: Cotmore Susan F. , Crowhurst Susan A. , Waterfield Michael D.
Published: February 2007

The purification and partial characterization of glycoproteins from human brain and fibroblasts which are antigenically and structurally related to the Thy‐1 glycoproteins of rats and mice is described. In addition, Thy‐1 molecules were isolated from the brains of AKR and CBA mice (Thy‐1.1 and Thy‐1.2, respectively). The molecules were purified from sodium deoxycholate extracts of brain tissue by chromatography on lentil lectin‐Sepharose followed by gel filtration, and purification was monitored by radioimmunoassay. Similar molecules were isolated from human brain and fibroblasts using monoclonal antibody columns. Analysis by electrophoresis on 12.5% polyacrylamide gels in sodium dodecyl sulfate (SDS) showed that Thy‐1‐related molecules from human brain migrate as a doublet with apparent molecular weights of 24700 and 26200. Thy‐1 from human foreskin fibroblasts cultured in vitro migrates as a single band of 26500. Thus, human Thy‐1 glycoproteins resemble their rat counterparts in exhibiting tissue‐specific polymorphism. Amino acid analysis of Thy‐1 from human brain and fibroblasts suggests that the polypeptides expressed by different tissues are extremely similar.

Thy‐1.1 from AKR mouse brain migrates as a doublet on SDS gel electrophoresis with apparent molecular weights of 23700 and 25100, while Thy‐1.2 molecules isolated from CBA mouse brain run as a single broad symmetrical band with a molecular weight of 25000. Molecules carrying the Thy‐1.1 allotype are readily distinguished from those carrying the Thy‐1.2 allotype by the presence of an additional arginine residue. Amino acid compositions of Thy‐1 from man and the two mouse strains are similar, but each has unique features.

Thy‐1 molecules immunoprecipitated from mouse and rat fibroblasts have higher apparent molecular weights than their brain counterparts; the basis of the tissue‐specific polymorphism is discussed.
Lambda chain expression at different stages of ontogeny in C57BL/6, BALB/c and SJL mice
Authors: Takemori Toshitada , Rajewsky Klaus
Published: February 2007

In C57BL/6 and BALB/c mice, 2–3% of immunoglobulin‐positive cells express λ1 and 1–2% λ2 chains at the cell surface. These percentages are constant from the time around birth until adult age. The levels of λ1 chains in serum antibodies correspond closely to those in the B cell population in both mouse strains whereas in the case of λ2 chains, they are three times lower in serum antibodies than in the B cell population.

In strain SJL, λ2‐bearing B cells occur in similar frequencies as in BALB/c and C57BL/6, both in newborn and adult animals. However, the level of λ2‐bearing immunoglobulins in the serum is 30 times below that expected on the basis of the cellular analysis and 10 times lower than in BALB/c and C57BL/6. B cells expressing λ1‐like light chains were found in normal frequency in newborn SJL mice with a monoclonal rat anti‐λ1 antibody. In adult animals such cells were present in a frequency 100 times below that characteristic for BALB/c and C57BL/6 mice. The concentration of immunoglobulin reactive with rat anti‐λ1 antibody was 300 times lower in SJL than in BALB/c and C57BL/6 serum, in accord with previous data (W. Geckeler et al., J. Exp. Med. 1978. 148: 1122).

The notion that in SJL mice a control mechanism specifically suppressess λ chain expression is further supported by an analysis of the early primary anti‐(4‐hydroxy‐3‐nitro‐phenyl)acetyl (NP) response. We show that this response is initially dominated by antibody‐forming cells secreting antibodies with λ1‐like light chains. These cells rapidly disappear and appear to be selected against particulary in the IgG response.

The monoclonal SJL anti‐λ1 antibody Ls136 (M. Reth et al., Eur. J. Immunol. 1979. 9: 1004) does not stain any B cells in SJL mice, whereas it detects λ1‐bearing cells in C57BL/6 and BALB/c animals in the expected frequency.
Anti‐receptor antibody‐induced suppression of murine H‐Y‐specific delayed‐type hypersensitivity responses
Authors: Sunday Mary E. , Weinberger Judah Z. , Wolff Stephen , Dorf Martin E.
Published: February 2007

A putative anti‐H‐Y receptor antiserum (ARA) was raised in C57BL/6 male mice against splenic T lymphocytes from syngeneic females immunized against H‐Y antigen. When this antiserum is given i.v. to C57BL/6 females it prevents the expression of H‐Y‐specific delayed‐type hypersensitivity (DTH). The suppressive activity in ARA was selectively retained on rabbit anti‐mouse immunoglobulin columns, and could be absorbed by H‐Y‐immune spleen cells from C57BL/6 female mice.

The abrogation of H‐Y DTH reactivity was at least in part due to the generation of suppressor T cells which are generated by ARA in naive female mice. ARA‐generated suppressor cells specifically ininhibit the induction phase of DTH responses to the H‐Y antigen, having no effect on (4‐hydroxy‐3‐nitrophenyl)acetyl (NP)‐specific cutaneous sensitivity responses or on DTH responses to minor histocompatibility antigens. Furthermore, there is a requirement for Igh gene homology between the strain producing the ARA and the strain in which the DTH response is induced. Thus, C57BL/6 ARA given to A.BY (H‐2b, Igh‐1e) or to B.C‐8 (H‐2b, Igh‐1a) mice was unable to suppress homologous H‐Y DTH responses in these strains. However, C57BL/6 ARA induced suppressor cells in B.C‐8 mice which were capable of inhibiting H‐Y DTH responses when adoptively transferred to C57BL/6 females.
Cytotoxic T cell recognition of Epstein‐Barr virus‐infected B cells. II. Blocking studies with monoclonal antibodies to HLA determinants
Authors: Wallace Lesley E. , Moss Denis J. , Rickinson Alan B. , McMichael Andrew J. , Epstein M. Anthony
Published: February 2007

Monoclonal antibodies specifically binding common determinants on all HLA‐A, B and C antigen molecules blocked the lysis of EB virus‐transformed target cells by EB virus‐specific cytotoxic T cells reactivated in vitro. Blocking was mediated through binding of the antibodies to the target rather than to the effector cells and was maximal (75 to 85% inhibition of lysis) at saturating antibody concentrations. A similar blocking effect was also shown by a monoclonal antibody binding to β2‐microglobulin, a molecule physically associated with HLA‐A, B and C antigens on the target cell surface, but not by a monoclonal antibody binding to the non‐HLA‐associated leukocyte‐common antigen. Saturating concentrations of monoclonal antibodies specific for common determinants on all HLA‐DRw antigen molecules either had no effect at all upon EB virus‐specific T cell cytotoxicity or caused a slight, but nonspecific, inhibition. The results demonstrate unequivocally that HLA‐A, B and C antigens on the target cell surface are indeed the polymorphic elements which impose genetic restriction upon EB virus‐specific cytotoxic T cell function.
T cell regulation of isotype expression The requirement for a second Ig‐specific helper T cell population for the induction of IgG responses
Authors: Rosenberg Yvonne J. , Asofsky Richard
Published: February 2007

A characteristic of the in vivo responses to T‐dependent antigens is the highly restricted expression of Ig heavy chain classes of both the antibody and nonspecific Ig produced. To investigate the cellular interactions which regulate expression of Ig class, sheep red blood cell‐ and keyhole limpet hemocyanin‐primed BALB/c T cells were tested in vitro for their ability to induce normal BALB/c B cells to selective Ig secretion. The results, based initially on linear regression analysis, indicate that while the production of IgM required help from a single antigen‐specific helper cell, additional signals from a second pool of helper cells were necessary for the expression of IgG isotypes. The greatly diminished ability of primed T cells from mice suppressed from birth for IgM production to induce IgG responses indicated that the generation of this second class‐regulating T cell pool requires the presence of Ig, probably B cell‐presented, during the period of priming.

Based on the present data, secretion of IgG by normal B cells can be explained by invoking the requirement for a second pool of helper T cells which recognize Ig determinants, in contrast to the I region recognition known to exist for effective help by the first helper cell. In addition, it is proposed that in the absence of such a second signal only IgM secretion will occur.
Regulation of antibody synthesis in the X‐irradiated Mexican axolotl
Authors: Charlemagne Jacques
Published: February 2007

The effects of X‐irradiation were studied on the Mexican axolotl antibody synthesis. To reduce the anti‐horse red blood cell (HRBC) antibody titers, 150 rd and smaller doses are ineffective, 200–450 rd are increasingly effective, and 700 rd are maximally effective (and lethal). A significant enhancement of the anti‐HRBC titers was observed in low doses (50–150 rd X‐irradiated animals). This enhancement was also observed when a low X‐ray dose was applied only on the thymic areas. In whole body, but thymus area‐shielded, 100 rd X‐irradiated animals, the anti‐HRBC titers were similar to those of the nonirradiated, HRBC‐immunized control group. To explain these phenomena, it is suggested that a radiosensitive, adult thymectomy‐sensitive and hydrocortisone‐sensitive suppressor T cell subpopulation regulates the antibody synthesis in the axolotl.
Binding of one monoclonal antibody to human Ia molecules can be enhanced by a second monoclonal antibody
Authors: Tosi Roberto , Tanigaki Nobuyuki , Sorrentino Rosa , Accolla Roberto , Corte Giorgio
Published: February 2007

A monoclonal anti‐human Ia antibody, PTF 29, was tested for its ability to bind purified, 125I‐labeled human Ia preparations. It was found that the binding level increases considerably in the presence of a second monoclonal antibody.

Experimental conditions were selected under which only the binding of PTF 29 and not the binding of the second antibody could be determined. Under these conditions, it was found that “helped” PTF 29 binding has higher affinity and is exerted on a molecular subset different from that bound by PTF 29 alone.

This phenomenon, while not easily accommodated in the present conceptual framework of the human Ia system, appears in itself interesting and may have more general implications.
Nomarski differential interference contrast studies of murine lymphocytes
Authors: Khalaf Ragaa M. F. , Bainbridge Douglas R.
Published: February 2007

Nomarski differential interference contrast microscopy (DIC) of lymphocyte surface morphology was combined with immunofluorescence studies of T and B cell markers on the thymus, lymph nodes, spleen, peripheral blood lymphocytes and thoracic duct lymph of female CBA mice. DIC identified smooth cells and several categories of villous cells; more extreme forms were present in lymph. Most B cells seemed to belong to the smooth group and most peripheral T cells to the villous group. Thymus cells were almost entirely smooth, but treatment with cortisone increased the proportion of villous cells to 50%.

The surface morphology of lymphocytes was highly labile preventing direct identification or separation of T and B cells. In vivo removal of T cells by adult thymectomy, lethal irradiation and bone marrow reconstitution caused the villous cells to decrease. During recovery from irradiation, T lymphocytes tended to parallel villous cells, B lymphocytes smooth cells, but there were differences between the spleen and lymph nodes.

Mice deprived of T1 cells by adult thymectomy showed a modest decrease of smooth cells in the spleen and blood; mice depleted of T2 cells by anti‐lymphocyte serum, or which were naturally deficient in T2 cells, were markedly lacking in villous cells. Thoracic duct lymph, which is rich in T2 cells, had a high proportion of extremely villous lymphocytes.

Exposure to lymph induced extreme villous features in lymph node cells, and it was found that the thoracic duct lymph was markedly hypertonic to serum, although varying in osmolarity throughout the day. It is suggested that the villous shape of T2 cells is a circulatory adaptation, necessitated by the peculiar character of the lymphatic system in mice.
The role of monovalent cations in the interaction between the cytotoxic T lymphocyte and its target
Authors: Russell John H. , Dobos Claraine B.
Published: February 2007

Evidence is provided for the participation of monovalent cations in both the binding and lytic phases of the lytic cycle. There appears to be one sodium requirement in the cytotoxic T lymphocyte‐target binding event (effective dose50 ∼ 35 mM) and possibly another sodium requirement in the delivery of the lethal hit (ED50 <7 mM). Potassium can replace sodium in the binding event but antagonizes the lethal hit phase (inhibitory dose50 ∼ 110 mM). Lithium antagonizes the binding event (ID50 ∼ 15 mM).
Antigen‐specific antibody response induced in cultures of human blood lymphocytes in presence of polyethylene glycol
Authors: Luzzati Alma L. , Ramoni Carlo , Ferrara Giovanni B.
Published: February 2007

Human peripheral blood lymphocytes respond in vitro to sheep red blood cells (SRBC) with the appearance of numerous specific plaque‐forming cells, if the Epstein‐Barr virus (EBV) is added to the cultures together with the antigen. However, it was found that when polyethylene glycol (mol. wt. 6000) is included in the culture medium at a final concentration of 4%, antigen alone is able to induce an anti‐SRBC response, with clear hemolytic plaques of regular size. Addition of EBV causes a further increase in the antigen‐specific antibody response.
Countercurrent distribution of human peripheral blood lymphocytes: isolation of a subpopulation enriched with natural killer and K cells
Authors: Levy Elinor M. , Zanki Steve , Walter Harry
Published: February 2007

Aqueous solutions of dextran and of poly(ethylene glycol) when mixed give rise to two‐phase systems suitable for the separation by partitioning of cells based on subtle differences in their membrane surface properties. Human peripheral blood mononuclear cells were obtained by centrifuging blood over Hypaque‐Ficoll and removing the cells from the cushion. Clean lymphocytes were then isolated by velocity sedimentation of the mononuclear cells. Lymphocytes were subjected to countercurrent distribution (i.e., a multiple extraction procedure) in a two‐polymer aqueous phase system which separates cells primarily on the basis of surface charge‐associated properties. It was found that a small subpopulation of cells with highest partition coefficient (presumably highest surface charge‐associated properties) contain virtually all of the natural killer (NK) and K cell activities.
Immunoregulatory circuits which modulate responsiveness to suppressor cell signals: contrasuppressor cells can convert an in vivo tolerogenic signal into an immunogenic one
Authors: Ptak Wlodzimierz , Green Douglas R. , Durum Scott K. , Kimura Art , Murphy Donal B. , Gershon Richard K.
Published: February 2007

The intravenous injection of 2,4,6‐trinitrophenyl (TNP)‐labeled peritoneal exudate cells (TNP‐PEC) into CBA mice fails to produce a state of hypersensitivity; rather, it renders recipient mice incapable of mounting a contact hypersensitivity response when they are subsequently immunized with a reactive form of the specific hapten. However, if precultured neonatal spleen cells are injected along with the cells that induce tolerance (TNP‐PEC), not only is the development of tolerance inhibited but sensitization to TNP develops. The neonatal spleen cell responsible for turning the tolerogenic signal into an immunogenic one is I‐J+ and adheres to the Vicia villosa lectin. Thus, it expresses markers that distinguish contrasuppressor effector cells from helper cells (D. R. Green et al., Eur. J. Immunol. 1981. 11: 973), indicating that activated contrasuppressor cells can act as potent, helpful regulatory cells in vivo.
Heterogeneity of stimulator cells in the murine mixed leukocyte response
Authors: Sunshine Geoffrey H. , Katz David R. , Czitrom Andrei A.
Published: February 2007

Mouse spleen cells were fractionated and tested for their ability to stimulate a primary mixed leukocyte response (MLR). Several nonlymphoid populations were stimulatory, purified dendritic cells and 18‐h adherent macrophages being the most effective. B and T lymphocytes and peritoneal washout cells were almost ineffective by comparison. This hierarchy of stimulator potential was observed whether the genetic difference between stimulator and responder was whole H‐2 or H‐2 subregion (K. D. I. I‐J). Allostimulatory populations contained a high proportion of cells expressing I region determinants. The functional importance of these antigens was confirmed using specific anti‐I region antisera. Thus, it appears that stimulator cells in the MLR are heterogeneous, Ia‐bearing, and of “accessory” rather than lymphoid type.
Expression of Qat‐4 and Qat‐5 alloantigens on cytotoxic precursor and effector cells: different surface phenotypes of alloreactive and H‐2‐restricted cytotoxic T Cells
Authors: Zahn Gabriele , Hämmerling Günther J. , And Klaus Eichmann , Simon Markus M.
Published: February 2007

Monoclonal anti‐Qat‐4 and anti‐Qat‐5 antibodies, which define antigens expressed on peripheral T cell subsets, have been used to study the phenotypes of alloreactive and H‐2‐restricted cytotoxic effector cells and their precursors. Depletion of Qat‐4+ or Qat‐5+ cells from the T cell pool prior to their sensitization in bulk cultures prevented the development of alloreactive and H‐2‐restricted cytotoxic activities in the selected populations. No reconstitution of cytolytic activities to normal levels was obtained when mixtures of Qat‐4+ and Oat‐5+ cells were sensitized in bulk cultures to H‐2 or non‐H‐2 antigens. Sensitization of limiting numbers of Qat‐4− or Qat‐5− lymphocytes under optimal conditions for help (interleukin 2), with the appropriate antigens (H‐2, H‐Y) did not result in the generation of cytotoxic T cells, indicating that the majority of all cytotoxic T lymphocyte (CTL) precursors are Qat‐4+, Qat‐5+.

When CTL effector populations were treated with the antisera and complement (C) at their maximum CTL activity, it was found that H‐2‐restricted CTL were totally eliminated by anti‐Qat‐4 and considerably reduced by anti‐Qat‐5 antisera and C. In contrast, alloreactive CTL effector cells were insensitive to anti‐Qat‐4 and to anti‐Qat‐5 plus c. Although alloreactive CTL effector populations regained some Qat‐4 antigens during further in vitro culture, it was shown that H‐2‐restricted CTL were at all times more sensitive to anti‐Qat‐4 than were alloreactive CTL. The findings suggest that during maturation of alloreactive and H‐2‐restricted CTL from their precursors, both alloantigens undergo differential quantitative variations in their expression that lead to different Qat‐4,5 phenotypes of alloreactive and H‐2‐restricted CTL.
Monoclonal antibodies OKT 11 and OKT 11A have pan‐T reactivity and block sheep erythrocyte “receptors”
Authors: Verbi Winston , Greaves Melvyn F. , Schneider Claudio , Koubek Kristian , Janossy George , Stein Harald , Kung Patrick , Goldstein Gideon
Published: February 2007

Monoclonal antibodies OKT11 (γ1) and OKT11A (γ2) are described and appear to have similar binding specificities. They bind, in immunofluorescence, with >95% of infant thymocytes, staining both cortical and medullary cells, 65‐80% of blood lymphocytes and selectively stain the T cell‐dependent paracortical areas of tonsil. A small proportion (9‐12%) of bone marrow lymphocytes stain, but this population excludes the terminal transferase‐positive cells.

Both the γ1 and γ2 antibodies stain the surface membrane Ig‐negative lymphocytes in blood and tonsil and are able to block sheep E rosette formation (to normal or leukemic T cells). In contrast, other monoclonal anti‐T reagents tested (OKT1, OKT3, OKT4, OKT6, OKT8, OKT9, OKT10) did not block E rosette formation. E rosette formation and OKT11 binding are coincident on T‐ALL cell lines and both are trypsin‐sensitive. In a series of 145 leukemias and 26 leukemic cell lines investigated, only leukemias with a T cell phenotype including E rosette positivity were reactive with OKT11 and OKT11A.

OKT11A binds to a polypeptide of approximately 50000 molecular weight on thymic lymphocytes. This structure may carry the recognition site for sheep erythrocytes. These antibodies provide additional useful markers for T cell analysis and are of potential therapeutic value.
T suppressor cells activated by anti‐Tsud serum are Igh‐V‐restricted
Authors: Owen Frances L. , Riblet Roy , Gottlieb Paul D.
Published: February 2007

T suppressor (Ts) cells can be activated by alloantiserum directed against Tsud, a cell surface marker associated with the Ts cell receptor for antigen. These cells are restricted in their ability to transfer suppression in allotype‐congenic mice. Transfer of suppression requires matching of donor and recipient mice at Igh‐V loci, but recipient mice need not share the Tsud allele nor the same allotype as the activated Ts cells. Genes linked to the kappa light chain locus apparently do not affect this transfer.
Human monoclonal autoimmune antibody produced in Vitro: rheumatoid factor generated by Epstein‐Barr virus‐transformed cell line
Authors: Steinitz Michael , Tamir Sara
Published: February 2007

The infection of selected lymphocytes from a rheumatoid arthritis patient with Epstein‐Barr virus resulted in an immortalized cell line that secretes a monoclonal rheumatoid factor (RF). The cloned line has been growing for more than 24 months, and constantly produces a monoclonal IgM, λ, 19 S, RF (1‐2 μg/ml/l06 cells).

The RF agglutinates human and rabbit IgG (but not IgM) and also protein A‐coated erythrocytes, but fails to do so to mouse, goat and swine IgG‐coated erythrocytes. When bound to immune complexes, this monoclonal RF does not bind complement. In the cell supernatant RF is the only immunoglobulin and it comprises approximately 5% of the total proteins. The affinity of RF to aggregated human IgG, as detected in inhibition experiments, is higher than that of Fe receptors found on human non‐T lymphocytes, K562 and Daudi cell lines.
Antigen‐independent, IgM‐induced antibody responses: requirement for “recurrent” idiotypes
Authors: Ivars Fredrik , Holmberg Dan , Forni Luciana , Pierre‐André  , Cazenave  , Coutinho Antonio
Published: February 2007

Anti‐idiotypic antibodies (a‐Id) were produced in syngeneic mice against two monoclonal IgM antibodies of BALB/c origin, TNP.11 and SP/603. In plaque inhibition tests, using IgM‐secreting hybridoma cells and anti‐idiotypic antibodies, these two IgM proteins, as well as the anti‐TNP myeloma protein MOPC 460 (IgA) were found to carry non‐cross‐reactive idiotypes.

Analysis of the anti‐trinitrophenyl (TNP) plaque‐forming cells (PFC) in BALB/c mice, either normal or immunized with TNP‐horse red blood cells, revealed that in addition to the MOPC 460 Id, also the SP/603 Id is recurrent and expressed by a fraction of the anti‐TNP antibody‐secreting cells in all individuals tested. In contrast, the TNP.11 Id could not be detected in any BALB/c mouse studied.

TNP.11 and SP/603 antibodies were then characterized by their ability to induce an antigen‐independent anti‐TNP response in normal BALB/c mice. While TNP.11 was found to be inactive, the same titers of SP/603 IgM induced antigen‐specific PFC all of which expressed the SPi603 Id, and increased titers of circulating IgM molecules carrying the same Id, suggesting that “recurrent” but not “nonrecurrent” Id are competent in this respect. A fraction of these SP/603‐induced, SP/603‐positive anti‐TNP antibodies also carried MOPC 460 Id, suggesting expression on the same molecule of idiotypic determinants found on independent non‐cross‐reactive “recurrent” idiotypes.
Demonstration at the single‐cell level of the existence of distinct clusters of epitopes in two predefined human Ia molecular subsets
Authors: Accolla Roberto S. , Sekaly Rafick P. , McDonald Audrey P. , Corte Giorgio , Gross Nicole , Carrel Stefan
Published: February 2007

The expression at the cell surface level of two previously defined human Ia antigen subsets, NG1 and NG2, was studied. Two monoclonal hybridoma antibodies, D1‐12 (anti‐NG1) and D4‐22 (anti‐NG2), labeled with distinct fluorochromes, were used as probes.

The results indicate that NG1 and NG2 molecules are simultaneously expressed on the same cell, and moreover, that they are identifiable as spatially separate structures. In addition, when a series of 6 other anti‐Ia monoclonal antibodies previously described were analyzed in a checkerboard test of binding inhibition at the cell surface level, they were found to closely mimic the reactivity pattern of either D1‐12 or D4‐22 antibody, suggesting that NG1 and NG2 Ia subsets express independent clusters of highly immunogenic epitopes.
Allotypes in Basilea rabbits
Authors: Weiss Siegfried , Garcia Irène , Jaton Jean‐Claude , Kelus Andrew S.
Published: February 2007

Basilea rabbits produce immunoglobulin molecules, practically all of which have λ light chains rather than x chains. This variant strain was derived from a homozygous (b9/b9) male. Sensitive serological methods revealed that at least some homozygous bas/bas individuals possess traces (about 100 ng/ml) of b9 molecules. This level usually increases to almost 1 μg/ml upon hyperimmunization with pneumococcal or streptococcal vaccines. One exceptional rabbit, with 50 μg/ml of b9 molecules, was found. In spite of the presence of b9 molecules in early pre‐immune bleeds, homozygous bas/bas rabbits produce strong anti‐b9 antibodies; i.e., they are capable of making autoantibodies. These anti‐b9 allotypic antisera were not distinguishable by our methods from routinely produced anti‐b9.
The effects of a monoclonal anti‐μ chain antiserum on the in vitro growth of normal B cells
Authors: Boyd Andrew W. , Pike Beverley L.
Published: February 2007

Membrane immunoglobulin (Ig) on B cells plays a role in specifically focusing antigen onto the cell surface. An unresolved question is whether the Ig receptor itself has the capacity to deliver a signal to the B cell, and if so what is the mechanism of that signal. To explore these questions we have developed a monoclonal rat anti‐mouse μ chain antibody (E4). In this study it is shown that protein A‐Sepharose‐purified monoclonal anti‐μ chain antibody inhibits proliferation of normal B cells in vitro even at the single cell level. This effect was independent of Fc receptor interactions. Furthermore, E4 was shown to inhibit lipopolysaccharide‐induced mitogenesis. These results provide evidence that interaction of antibody with only a single determinant on the Ig receptor can deliver a negative signal to the B cell.
Demonstration of two distinct light chains in HLA‐DR‐associated antigens by two‐dimensional gel electrophoresis
Authors: De Kretser Theonne A. , Crumpton Michael J. , Bodmer Julia G. , Bodmer Walter F.
Published: February 2007

The polypeptide composition of HLA‐DR‐associated antigens was analyzed by two‐dimensional nonequilibrium pH gradient electrophoresis (NEPHGE)/sodium dodecyl sulfate (SDS)‐polyacrylamide gel electrophoresis (PAGE). Glycoprotein fractions from B lymphoblastoid cell lines homozygous for the DR antigen were used as antigen source. The HLA‐DR‐associated antigens were isolated by immunoprecipitation using a monoclonal anti‐DR antibody, TDR31.1. Two polypeptides corresponding in molecular weight to the HLA‐DR‐associated antigen β chain were detected. These polypeptides were shown to be different molecules on the basis of their separation on NEPHGE/SDS‐PAGE analysis, their rates of turnover relative to the other polypeptides of the HLA‐DR‐associated antigens, and their noncoordinate alteration in position on NEPHGE/SDS‐PAGE two‐dimensional analysis of different cell lines. Of the two β polypeptides, only one was invariant in position on NEPHGE/SDS‐FAGE analyses of cell lines homozygous for the same DR specificity. It appears therefore that the position of one of these β polypeptides correlates with DR specificity, while the other β polypeptide exhibits positional variation on NEPHGE/SDS‐PAGE analysis, indicative of polymorphism at a second HLA‐DR‐associated locus.
T‐T cell interactions during cytotoxic T cell responses IV. Murine lymphoid dendritic cells are powerful stimulators for helper T lymphocytes
Authors: Röllinghoff Martin , Pfizenmaler Klaus , Wagner Hermann
Published: February 2007

Enriched populations of Ia+ Fc receptor‐negative dendritic cells were compared to other cell types for their stimulatory activity in primary mixed lymphocyte reactions to alloantigens and 2,4,6‐trinitrophenylated syngeneic cells. Dendritic cells were 20‐100 times more effective than unfrationated splenocytes. A second cell type exhibiting strong stimulatory activity was an Ia+ Fc receptor‐positive transiently adherent cell. Both types of stimulatory cells were only effective when able to produce the monokine interleukin 1. Thus glutaraldehyde‐fixed cells were not stimulatory unless extraneous interleukin 1 was added. Stimulation of helper cells by either dendritic cells or Ia+ Fc receptor‐positive cells resulted in the production of interleukin 2. The data are discussed in view of the recently formulated interleukin model as a minimal scheme to explain T‐T cell interactions during the in vitro induction of cytotoxic T lymphocytes.
Patterns of isotype expression by B cell clones responding to thymus‐dependent and thymus‐independent antigens in vitro
Authors: Hurwitz Julia L. , Tagart Victoria B. , Schweitzer Peter A. , Cebra John J.
Published: February 2007

It was found that the Type 2 thymus‐independent (TI‐2) antigens bacterial levan, trinitrophenyl‐Ficoll, and pneumococcal carbohydrate vaccine (PnC) stimulate clonal expansion and antibody secretion in splenic fragments from either hemocyanin‐primed or unprimed irradiated recipients bearing B cells from unprimed donors. The in vitro stimulation with TI‐2 antigens leads to the expression of isotype switching and provides a more balanced variety of isotypes than is usually observed in vivo. Still, some characteristic patterns of isotypes expressed in vivo to either TI‐2 or thymus‐dependent (TD) antigens are preserved in vitro. Frequencies of phosphocholine (PC)‐reactive B cells responding to either PnC or to PC‐hemocyanin (PC‐Hy) suggest an appreciable overlap in populations responding to these TI and TD forms of antigen. The existence of a population responsive to either form of PC determinant is supported by the observation that many clones arising in the presence of both forms of antigen express patterns of isotypes that appear as summations of those distinct patterns shown by clones responding to only one form or the other. These data suggest that PC‐Hy‐ and PnC‐responding cells may derive from a linear rather than a branched pathway of B cell development and that expression of isotype switching over the lifetime of a developing B cell clone may be regulated in a manner dependent on the form of the stimulating antigen.
Quantitative studies of the secretion of complement component C3 by resident, elicited and activated macrophages. Comparison with C2, C4 and lysosomal enzyme release
Authors: Zimmer Bernd , Hartung Hans‐Peter , Scharfenberger Georg , Bitter‐Suermann Dieter , Hadding Ulrich
Published: February 2007

To quantitate the secretion of complement component C3 by guinea pig peritoneal macrophages an enzyme‐linked immunosorbent assay was developed. C3 secretion was studied in resident, elicited and activated macrophages and compared with release of hemolytically active C2 and C4, as well as the lysosomal enzyme β‐D‐2‐acetamido‐2‐deoxyglucosidase.

Resident macrophages secreted about 6 ng C3/106 cells/h into culture supernatants over a period of 12 h. Corynebacterium parvum‐activated cells were found to secrete 3 times that amount at nearly constant rates. There was a stepwise increase in secretion of functional C2 and C4 when comparing resident, elicited and activated macrophages; secretion was 2‐4 times higher in activated than in resident cells.
Synthesis of λ1, λ2, and λ3 light chains by mouse spleen B cells
Authors: Reilly Edward B. , Frackelton A. Raymond , Eisen Herman N.
Published: February 2007

To determine whether the infrequency of immunoglobulins with λ3 light chains is due to a corresponding scarcity of λ3 B cells, the production of the various λ chain subtypes (λ 1, λ2, and λ3) by normal spleen cells was compared. The results showed that λ1, λ2, and λ3 chains are produced in a ratio of about 1.0 :0.7 : 0.3, respectively. The argument is made that λ1, λ2, and λ3 B cells exist in the same ratio. Results obtained with neonatal and nude mouse spleen cells suggest that these small differences are not due to stimulatory effects of environmental antigens or regulatory T cells. The much greater disparity in the abundance of λ subtypes in various antibody responses and serum Ig suggests that λ1 B cells may be more likely than λ2 or λ3 B cells to differentiate into antibody‐secreting plasma cells.
Expression of cell surface lectins on activated human lymphoid cells
Authors: Apgar John R. , Cresswell Peter
Published: February 2007

A cell surface lectin found on activated human lymphoid cells has been identified and characterized using membrane glycoprotein micelles as probes. These micelles, which are large, water‐soluble aggregates, are composed of glycoproteins isolated from detergent‐solubilized membranes of human B lymphoblastoid cell lines by Lens culinaris hemagglutinin affinity chromatography. The micelles have an average apparent molecular weight of 4 × 106 estimated by gel filtration and range in diameter from 25‐100 nm. Micelles bind to B and T lymphoblastoid cell line cells and peripheral blood lymphocytes activated with concanavalin A or in a mixed lymphocyte response. Unactivated peripheral blood lymphocytes and red blood cells bind very low levels of the micelles. The binding is saturable, reversible, and temperature‐dependent, with poor binding below 15 °C. Glycoproteins such as fetuin and porcine thyroglobulin, which contain complex oligosaccharide side chains, inhibit the binding, whereas glycoproteins containing only high mannose or simple serine‐linked carbohydrate side chains do not. In addition, binding can be inhibited by complex asparagine‐linked glycopeptides purified from pronase‐digested fetuin, but not by the simple serine‐linked glycopeptides. Membrane glycoprotein micelles are bound to the surface of the cells but are not internalized or degraded. The potential role of this cell surface lectin in lymphocyte function is discussed.
Postirradiation thymocyte regeneration after bone marrow transplantation. III Intrathymic differentiation and development of thymocyte subpopulations
Authors: Boersma Wim J. A. , Kokenberg Esther , van der Westen Gerard , Haaijman Joost J.
Published: February 2007

Fluorescence distributions of thymocytes stained for Thy‐1 as well as size measurements were used to discriminate between thymocyte subpopulations during regeneration of the thymus after irradiation and bone marrow transplantation.

Subpopulations with “low” and “high” Thy‐1 density of donor‐ and recipient‐derived progeny were quantitated. They were continuously present in the thymus and developed simultaneously but at different rates of growth. A similar developmental pattern was observed for donor‐ and host‐derived “high” Thy‐1+ cells, whereas “low” Thy‐1+ cells of donor and recipient origin showed markedly different growth patterns. This indicated that development of the two subpopulations took place independently. During early regeneration donor‐derived “low” and “high” Thy‐1+ cells contain a high proportion of large cells, indicating the presence of cycling cells in both subpopulations.
A monoclonal antibody recognizing a human thymus leukemia‐like antigen associated with β2‐microglobulin
Authors: Knowles Robert W. , Bodmer Walter F.
Published: February 2007

A monoclonal antibody, M241, was produced which binds to a human cell surface molecule with properties similar to the murine thymus leukemia (TL) antigen. This human TL‐like antigen was found on thymocytes and some T cell lines derived from patients with acute lymphocytic leukemia, but was not found on peripheral blood lymphocytes or B cell lines. The monoclonal antibody M241 was used to immuno‐precipitate a molecule from lysates of 125I surface‐labeled MOLT 4 cells which had two subunits, a 43‐kDa chain and a 12‐kDa chain. The small subunit was shown to be β2‐microglobulin (β2m) by immunoprecipitation with a monoclonal antibody, BBM.1, which recognizes human β2m. The TL‐like molecule recognized by M241 was shown to be serologically distinct from the HLA‐A, B, C molecules recognized by three monoclonal antibodies W6/32, PA2.6 and BB7.8, and distinct from another human thymocyte antigen, the 49 kDa HTA 1 molecule, recognized by the monoclonal antibody NA1 / 34. Following removal of the HLA‐A, B, C molecules, the HTA 1 molecules, and the M241‐defined TL‐like molecules from MOLT 4 lysates, additional β2m‐associated molecules were immunoprecipitated with BBM.1. These molecules contained a 45‐kDa subunit attached to β2m.