bluuebunny/crossref_metadata_2025 huggingface dataset:
Education of human lymphocytes against mouse cells: specific recognition of H‐2 antigens
Authors: Carnaud C. , Fadaï‐Ghotbi M. , Lesavre P. , Bach J.‐F.
Published: February 2007

Xeno‐sensitization of human peripheral blood lymphocytes (PBL) against mouse lymphoid cells has been studied in vivo in a local graft‐vs. ‐host (GVH) assay and in vitro in a mixed lymphocyte culture‐cell‐mediated lympholysis system. Human PBL were injected into the footpads of mice rendered unresponsive by total‐body irradiation, and these were subsequently tested for the presence of cytotoxic cells in the draining popliteal lymph node (LN). In spite of a definite PBL‐induced LN proliferation, no cytotoxic activity was detected against mouse target cells. In contrast with the GVH assay, human PBL collected after 7 days of in vitro culture in the presence of irradiated mouse cells, were strongly cytotoxic against mouse target cells. The antigenic specificities recognized by in vitro educated cells were primarily those coded for by the H‐2 complex. Only target cells with an H‐2 haplotype identical to that of the sensitizing mouse strain or with at least an H‐2 D end in common with that strain were killed by xeno‐sensitized lymphocytes. Mouse target cells derived from congenic resistant strains remained unaffected. It was verified that in vitro educated PBL depleted of B cells retained their cytotoxic effect, indicating that non‐B cells and probably T cells were involved in the response.
Correlation between structural characteristics and immunological properties of the terpolymer L‐glutamic acid60‐L‐alanine30‐L‐tyrosine
Authors: Théze J. , Waltenbaugh C. , Benacerraf B.
Published: February 2007

The structure of the terpolymer L‐glutamic acid60‐L‐alanine30‐L‐tyrosine10 (GAT) has been investigated. GAT appears very heterogeneous in size as determined by gel filtration on a Sephadex G‐1 00 column. A dramatic downward shift in the average molecular weight (m.w.) is observed after gel filtration under denaturing conditions (Sepharose 6B, 6 M guanidine hydrochloride or polyacrylamide gel electrophoresis containing 0.1 % sodium dodecyl sulfate). We conclude that under nondenaturing conditions, GAT is a multimeric structure; the dissociation of the structure is reversible. GAT was fractionated based on the size of the polypeptide chains under denaturing conditions. After removal of guanidine hydrochloride three fractions were obtained with ∼ 100 000 (GAT fraction I), 45 000 (GAT fraction II) and < 10 000 (GAT fraction III) m.w., respectively.

The immunological properties of these three fractions have been compared with those of unfractionated GAT. Fraction II resembles unfractionated GAT, showing similar immunogenicity in responder mice and suppressive properties in nonre‐sponder animals. Fraction I is less immunogenic, otherwise it resembles unfractionated GAT. Fraction III is the most dissimilar of the three fractions investigated. It retains the suppressive activity of GAT but is unable to stimulate a specific antibody response in responder animals. GAT fraction III is not a general tolerogen and is specifically suppressive for nonresponder mice.
VH and L‐chain allotype determinants of rabbit IgG and IgA estimated by a semi‐automatic, modified Farr‐type radioimmunoassay
Authors: Jensenius J. C.
Published: February 2007

A sensitive radioimmunoassay for rabbit immunoglobulin allotypes has been developed. Separation of antibody‐bound and free antigen was accomplished by salt precipitation with ammonium sulfate, followed by collection and wash on glass fiber filters by means of a semi‐automatic cell harvester. The efficiency of the collection was increased by the addition of nonionic detergent which was salted out together with the precipitated reagents. The presentation of the a1 allotype, located in the VH region, was found to be different on IgG and IgA molecules.
Mechanism of target cell lysis by cytolytic T lymphocytes. Characterization of specific lymphocyte‐target cell conjugates separated by velocity sedimentation
Authors: Cerottini J.‐C. , Ryser J.‐E. , Sordat B. , Brunner K. T.
Published: February 2007

Differential velocity sedimentation was applied for separating alloimmune T lymphocytes bound to target cells (TC) from free lymphocytes. Maximal size differences between lymphocytes and TC were achieved a) by isolating the fraction of small peritoneal lymphocytes (SPL) from an alloimmune peritoneal cell population, and b) by selecting large tumor cells as TC. Under the conditions used, most of the conjugates formed at room temperature consisted of one SPL bound to one TC, and adequate separation of bound from free SPL could be achieved within less than 5 min.

Functional studies of the conjugate‐enriched fractions showed that a minimum of 60 % of TC‐bound SPL were indeed cytolytic. Conjugate‐depleted fractions, however, were still lytic, suggesting that not all effector cells formed stable conjugates at room temperature. Transmission and scanning electron microscopy studies revealed that binding between SPL and TC was achieved through interpenetrating membrane projections and was characterized by point and broad zone contacts. When lysis was allowed to proceed, prominent changes of the TC membrane morphology, including loss of microvillous projections, appearance of localized blebs, pseudopod‐like projections, and membrane defects were documented.
Lymphokine‐induced secretion of plasminogen activator by murine macrophages
Authors: Klimetzek V. , Sorg C.
Published: February 2007

Thioglycollate‐stimulated macrophages are known to release a plasminogen activator (PA) into the medium. In this study it was investigated whether macrophages could be activated to release PA after exposure to lymphokines. Macrophage monolayers obtained by 24 h culture of proteose peptone‐elicited murine exudate cells were incubated with lymphocyte culture supernatants. After 48 h the supernatants were replaced by serum‐free medium and the macrophages were incubated for another 24–48 h. These supernatants were assayed for PA as measured by the lysis of 125I‐labeled fibrin. The following results were obtained:

(a) Supernatants of antigen or mitogen‐stimulated spleen cells induced PA secretion by macrophages whereas control supernatants were ineffective. The same was found with supernatants of mitogen‐stimulated lymph node cells.

(b) PA secretion by macrophages seems to be induced by a rather narrow concentration range of lymphokines.

(c) Lymphokine‐induced PA secretion by macrophages is enhanced after phagocytosis of latex beads. The results show that PA secretion by activated macrophages can be considered as a parameter of immunoactivation.
Effect of in vivo stimulation of mice on the secretion of factor B of the alternative complement pathway by peritoneal macrophages
Authors: Bentley Carolyn , Hadding U. , Bitter‐Suermann D. , Brade V.
Published: February 2007

After in vivo treatment of mice with thioglycollate medium, the amount of native factor B which could be detected in vitro in culture supernatants of peritoneal macrophages was much lower than that found in supernatants of macrophages taken from untreated mice. However, when the macrophages from thioglycollate medium‐treated mice were cultured on a plastic surface covered with glutardialdehyde‐linked bovine serum albumin, the culture supernatants contained larger quantities of native factor B than culture supernatants of macrophages from untreated mice under the same conditions. Thus, the effect of in vivo thioglycollate medium treatment on the in vitro secretion of factor B by peritoneal macrophages could be modulated by the culture conditions. Factor B in culture supernatants of macrophages obtained from both untreated and thioglycollate medium‐treated mice was stable. It remained functionally active, and therefore uncleaved over a long incubation period at 37 °C. In addition, factor D activity was never detected in any culture supernatant.
Loss of surface IgD by human B lymphocytes during polyclonal activation*
Authors: Preud'Homme J.L.
Published: February 2007

Surface and cytoplasmic immunoglobulins were studied by direct immunofluorescence in pokeweed mitogen‐stimulated cultures of human blood lymphocytes. The results compared to those of studies of unstimulated cultures and of fresh normal lymphocytes showed a striking decrease in surface IgD during terminal maturation of B lymphocytes into plasma cells. The number of cells which expressed IgG Fc receptor also decreased, although to a lesser extent.
IgA antibody response to intragastric immunization in high and low immune responder lines of mice
Authors: André C. , Bazin H. , Biozzi G.
Published: February 2007

Two lines of mice selected for genes controlling the character “quantitative agglutinin production” to heterologous erythrocytes were immunized orally by the intragastric administration of sheep red blood cells (SRBC). The quantity of circulating IgA anti‐SRBC and the numbers of splenic plaque‐forming cells of IgA and IgM classes were related to the genetic status of the animal lines.
The induction of carrier‐specific helper cell tolerance in presensitized rats
Authors: Sanfilippo F. , Scott D. W.
Published: February 2007

Lewis rats rendered tolerant to sheep IgG (SGG) show a markedly reduced antibody response to the 2,4,6‐trinitrophenyl (TNP) hapten when later challenged with TNP‐SGG. We have previously shown that this effect is due to functional unresponsiveness in the carrier SGG‐specific helper T cell population. In this paper we demonstrate that induced helper cell tolerance is also maintained through a secondary immunogenic challenge. Furthermore, rats which are primed to the carrier SGG prior to tolerance induction also show a markedly reduced anti‐TNP response upon secondary immunogenic challenge with TNP‐SGG. The ability to specifically suppress a secondary response in this manner was found to be relatively long lasting, since rats showed reduced responsiveness when the secondary challenge was delayed for up to 4 weeks after tolerance induction. In addition, rats primed to the hapten (TNP) prior to carrier (SGG) tolerance induction also showed a marked reduction in anti‐TNP antibody following challenge with TNP‐SGG. These findings imply that helper cell tolerance can be induced in rats even after priming of carrier‐specific (SGG) helper cells, or hapten‐specific (TNP) B cells. These results parallel our other published findings that IgE responses in presensitized rats can be overcome by helper cell tolerance.
Genetic defect in responsiveness to the B cell mitogen lipopolysaccharide
Authors: Coutinho A. , Forni Luciana , Melchers F. , Watanabe T.
Published: February 2007

Splenic B cells from C57BL/10ScCr mice fail to respond to the mitogenic principle of lipopolysaccharide (LPS), and do not express a serologically defined “LPS receptor”. In contrast, polyclonal B cell responses to both purified protein derivative of tuberculin and lipoprotein are conserved.
Mercuric chloride‐induced anti‐glomerular basement membrane antibodies in the rat Genetic control
Authors: Druet Elvira , Sapin C. , Günther E. , Feingold N. , Druet P.
Published: February 2007

Mercuric chloride induces anti‐glomerular basement membrane antibodies in the Brown‐Norway rat. Various other inbred rat strains (Lewis, Wistar AG, August, PVG/c) were not found t o be able to produce such antibodies under the same experimental conditions. Hybrids (F1, F2 and F1 × LEW) were bred from Brown‐Noway and Lewis rats and injected with mercuric chloride. It has been demonstrated that the induction of anti‐glomerular basement membrane antibodies by mercuric chloride in these crosses is under genetic control. The response was found t o depend on two or three genes one of which was H‐1‐linked. The negative results obtained with L.BN congenic rats were in complete agreement with this conclusion.
Mechanisms of B cell tolerance
Authors: Klaus G. G. B. , Abbas A. K. , Mcelroy P. J.
Published: February 2007

The experiments reported examined the fate and properties of antigen‐binding B cells (ABC) during the induction of hapten‐specific tolerance by 2,4‐dinitrophenyl (DNP)‐conjugated type 3 pneumococcal polysaccharide (S3). We found that (a) after short (nontolerogenic) pulses of DNP‐S3, anti‐DNP Ig receptors were physically blocked by cell‐bound antigen. Removal of extracellular tolerogen led to full functional recovery of ABC. (b) After more prolonged (tolerogenic) exposures to DNP‐S3 the degree of recovery of ABC following antigen‐free culture was inversely related to the dose of antigen given, (c) Regardless of the dose or duration of exposure to DNP‐S3, cells initially binding antigen effectively cleared it from their membranes; after tolerogenic exposures, cells neither carried cell‐bound DNP‐S3, nor expressed functional receptors, (d) Under conditions where tolerized cells recovered near normal levels of ABC after removal of extracellular antigen, these ABC appeared to display fewer receptors per cell than normal.

We therefore propose that B cell inactivation by DNP‐S3 involves the progressive and eventually irreversible inhibition of Ig receptor expression on DNP‐reactive B cells, and is not due to stable blockade of receptors by cell‐bound antigen. The relationship of this effect to other models of B cell inactivation (especially the similar phenomenon seen in immature B cells exposed to anti‐receptor antisera) is discussed.
Effect of tumor cells on the generation of cytotoxic T lymphocytes in vitro
Authors: Koran H. S. , Hodes R. J.
Published: February 2007

In agreement with previous reports, the primary in vitro response to alloantigens has been shown to be dependent on the presence of macrophages (Mphs). Splenocytes extensively depleted of adherent phagocytic cells did not generate cytotoxic T lymphocytes, and this activity could be completely restored by small numbers of adherent peritoneal cells (accessory cells).

Either P388D1 (Mph‐like tumor), P388 (“null” tumor) orP815 (mastocytoma) tumor cells, or 2‐mercaptoethanol, could completely replace the accessory function normally mediated by accessory cells. These tumor cells did not non‐specifically “enhance” the cytotoxic activity generated with normal nonde‐pleted spleen cells. The restored cultures maintained killing specificity to H‐2 targets which was mediated by effector T cells as shown by sensitivity to anti‐Θ and complement.

Therefore, Mphs seem not to be the sole cells capable of mediating an accessory function in a primary response to alloantigens in vitro.
Lymphocytes which differentiate in an allogeneic thymus
Authors: Kindred Berenice , Sordat B.
Published: February 2007

Nude mice which have been grafted with an allogeneic H‐2‐incompatible thymus are frequently specifically tolerant to skin grafts from the thymus donor strain. The evidence presented here indicates that both clonal deletion and peripheral suppressor cells play a part in maintaining this tolerance.
Ia‐bearing cells promote the concanavalin A mitogenic response of la‐negative T cells
Authors: Frelinger J. A.
Published: February 2007

Nylon wool column‐purified T cell populations depleted of la‐bearing cells do not respond to the T cell mitogen concanavalin A (ConA). The response of this population can be restored by admixture of untreated nylon wool‐nonadherent T cells. These promoter cells express Thy‐1, are not sensitive to mitomycin C treatment and cannot be replaced with adherent spleen cells. Experiments using the T6 chromosome marker demonstrate that Ia‐depleted populations respond to ConA only in the presence of the Ia‐positive population.
B lymphocyte development in fetal liver
Authors: Melchers F.
Published: February 2007

Single cell suspensions of fetal liver cells, prepared from embryos at day 13 of gestation until birth, develop mitogen bacterial lipopolysaccharide (LPS)‐reactive B cells “in vitro” within the same time as they do “in vivo”. The development of these mitogen LPS‐reactive B cells in vitro is dependent on unknown components of fetal calf serum, found in some but not all batches. It does not require the presence of the corresponding B cell mitogens, i.e. LPS, in culture. Fetal liver cells, put in culture at different times of gestation, all acquire LPS reactivity at the equivalent of birth in vitro. When the cells have become LPS‐reactive, they are then stimulated by LPS to growth and maturation into clones of IgM‐secreting, IgA‐secreting and IgG‐secreting plaque‐forming cells (PFC). The development of these PFC responses is mitogen‐dependent: in the absence of LPS only 2‐5 % of the LPS‐stimulated PFC responses develop. Only the magnitude, but not the development in time, of LPS reactivity of fetal liver cells is different in vivo and in vitro. This may indicate either that an early precursor cell to LPS‐reactive B cells can only divide in vivo but not in vitro, or that early precursors continue to migrate with time of gestation into fetal liver. After birth B cells in liver are immediately reactive to LPS; however, they rapidly leave the liver.

Few, if any, dextrans sulfate or lipoprotein‐reactive B cells, yielding a PFC response, develop in fetal liver cells either in vivo or in vitro. Neonatal spleen contains immediately mitogen‐reactive B cells. Comparable numbers of LPS, dextran sulfate and lipoprotein‐reactive cells are found.

Development of fetal liver cells to Ig‐secreting PFC, occurs, therefore, in two stages. The first (pre‐B → B) is independent of externally added mitogen (such as LPS), the second (B → PFC) requires the addition of mitogen. The majority of spleen cells have already passed this first stage of development.
Genetic variation in antibody response and natural killer cell activity against a Moloney virus‐induced lymphoma (YAC)
Authors: Åsjö Birgitta , Kiessling R. , Klein G. , Povey Susan
Published: February 2007

Antibody formation against the Moloney virus‐determined surface antigen (MCSA) was found to be under genetic control. In the (A × C57BL)F1 cross one dominant gene played a major role, resulting in bimodal distribution of the antibody response. This gene showed no linkage to H‐2, IgG heavy chain immunoglobulin allotype, the coat color markers B and C, and five different isozyme markers representing chromosome numbers 1,4,7,8 and 9. Antibody response to MCSA was not correlated with antibody titers against the virion proteins, confirming that MCSA was an independent entity. There was no relationship between the segregation of natural killer cell activity and antibody response in a [(A × C57BL) × A] backcross population.
Inhibition of lymphocyte proliferation by factor(s) produced by Schistosoma mansoni
Authors: Dessaint J.P. , Camus D. , Fischer E. , Capron A.
Published: February 2007

Normal spleen cells of CBA mice or Fischer rats were cultured with mitogens or allogeneic cells, together with various substances of Schistosoma mansoni origin, and thymidine uptake was measured. The proliferation (DNA synthesis) of normal lymphocytes was inhibited by the incubation product of the parasite as well as by cell‐free supernatant of schistosome culture. Inhibition was obtained only when active materials were added at the beginning of the culture. Both T and B cell proliferation were inhibited. The inhibitory activity found in cell‐free supernatant suggested the release by the parasite of some factor(s) interfering with lymphocyte proliferation. Moreover, serum from rats infected by S. mansoni inhibited lymphocyte proliferation also. The inhibitor(s) appeared heat resistant, dialyzable and of low molecular weight (500–1000). Incubation of normal spleen cells with S. mansoni inhibitor(s) did not enhance the release of nonspecific suppressor cell factor. The inhibition product(s) released by the parasite could explain part of the immunosuppression status found in schistosomiasis.
Role of epitope density in the induction of immunity and tolerance with thymus‐independent antigens IV. Selective tolerance of IgE response by DNP‐levan conjugates
Authors: Desaymard Catherine
Published: February 2007

Tolerance induction of IgE antibody‐forming cells by dinitrophenylated levan (DNP‐LE) conjugates was investigated in CBA mice. Antibody production was measured by passive coutaneous anaphylaxis on rat skin. Specific antibody neutralization was obtained with conjugates of different substitution degrees. Specific inhibition of IgE antibody production was obtained only with highly substituted conjugates. However, the epitope density required for inducing tolerance to antibody synthesis of the IgE class was lower than for other classes of immunoglobulins. The tolerance induced by DNP‐LE was shown to affect only the anti‐DNP B cells of IgE class without T cell participation.

These results demonstrate that B cell precursors of all Ig classes are susceptible to tolerance induction and not to triggering by T‐independent antigens.
Evidence for a similar or common mechanism for natural killer cell activity and resistance to hemopoietic grafts
Authors: Kiessling R. , Hochman Paula S. , Haller O. , Shearer G. M. , Wigzell H. , Cudkowicz G.
Published: February 2007

Two types of host reactivities not requiring immunization in the mouse and not mediated by T lymphocytes were compared: resistance of irradiated and nonirradiated F1 hybrids to accept parental grafts of normal or malignant hemopoietic cells (Hh system), and the natural killer cell activity against mouse lymphomas (NK system). The effects of six independent variables known to influence resistance to marrow grafts were investigated in the NK system using YAC‐1 lymphoma cells as targets. The following properties were shared: (a) maturation during the fourth week of life; (b) low sensitivity to acute total body irradiation; (c) dependence on the integrity of bone marrow as demonstrated by reduced reactivity in 89Sr‐treated mice; (d) suppression by a single injection of rabbit anti‐mouse bone marrow serum; (e) suppression by a single injection of the anti‐macrophage agents silica and i‐carrageenan; and (f) suppression by multiple injections of parental spleen cells into F1 mice. These positive correlations are particularly significant because most of the variables have either opposing or no effect on conventional immunity. F1 mice rendered specifically unresponsive to parental marrow grafts, could retain NK cell activity, and genetically susceptible mice could be rendered hyporeactive in terms of NK cells, indicating that the specificities of YAC‐1 and Hh‐1 incompatible targets were different.

It is extremely unlikely that this remarkable parallelism is fortuitous. These results indicate that either a very similar, or more likely a common mechanism is operative in the two cell‐mediated natural reactivities: effector cells in the NK and Hh systems do not bear B or T lymphocyte markers but are nevertheless endowed with “specificity”. They are dependent for generation in vivo (presumably by maturation or by recruitment) on the interaction with nonlymphoid accessory cells not endowed with specificity, capable of also interacting in vitro with Thy‐1‐positive F1 hybrid prekiller cells specific for parental targets. Because of thymus independence in vivo and apparent restriction to target cells of the hemopoietic system, these reactivities should be effective in the regulation of hemopoiesis and surveillance over leukemogenesis.
A myeloma hybrid producing antibody specific for an allotypic determinant on “IgD‐like” molecules of the mouse
Authors: Pearson T. , Galfrè G. , Ziegler A. , Milstein C.
Published: February 2007

A hybrid cell line was produced by fusing a mouse myeloma line with spleen cells from BALB/c mice immunized with B10 cells. The hybrid line grew in tissue culture and in syngeneic mice and produced IgM antibody specific for “IgD‐like” molecules of mice with the Igb haplotype. The concentration of monoclonal antibody in the serum of tumor‐bearing animals reached about 2 mg/ml and gave cytotoxic titers of up to 1:800 000. The derivation of the line, some properties of the antibody secreted and the nature of its antigenic target aredescribed.
Immunosuppressive factor(s) specific for L‐glutamic acid50‐L‐tyrosine50 IV. In vitro activity and immunochemical properties
Authors: Thèze J. , Waltenbaugh C. , Germain R.N. , Benacerraf B.
Published: February 2007

The responsiveness of BALB/c spleen cells to the terpolymer L‐glutamic acid60‐L‐alanine30‐L‐tyrosine10(GAT), the copolymer of L‐glutamic acid50‐L‐tyrosine50 (GT) and the corresponding complexes with methylated bovine serum albumin (MBSA) has been studied in vitro in a modified Mishell‐Dutton culture system, Cultures of BALB/c spleen cells respond to GAT, GAT‐MBSA and GT‐MBSA over a wide dose range. Contrary to in vivo findings BALB/c spleen cell cultures respond to GT in vitro although in a much narrower dose range. Lymphoid extracts from GT‐primed BALB/c or B10.BR mice (GT‐TSF) specifically suppress the GT‐MBS A response in vitro. This culture system has allowed us to further investigate immunochemical properties of both BALB/c and B10.BR GT‐TSF. GT‐TSF from both strains display affinity for GT‐Sepharose and bear determinants encoded by the I region of the H‐2 complex. Moreover, we demonstrate that the suppressive activity from B10.BR mice is a molecule or a molecular complex which displays affinity for GT and bears determinants of the I‐J subregion of the H‐2k haplotype.
B cell antigens on effectors for natural cell‐mediated cytotoxicity
Authors: Koide Y. , Takasugi M. , Billing R.
Published: February 2007

Cell suspensions enriched for N cells, the effector cell for human natural cell‐mediated Cytotoxicity, were observed t o react strongly with a rabbit antiserum directed against an antigen associated with B cells. Treatment of the effector suspension with the antiserum resulted in inhibition of natural cell‐mediated cytotoxicity. The blocking occurred, however, only with the intact antibody indicating that inhibition was caused through the formation of antigen‐antibody complexes. The antiserum was then employed t o arm natural effector cells to react specifically with B cell lines. Specific arming was achieved after the formation of antigen‐antibody complexes was prevented by initially reacting the effector suspension with F(ab′)2 of the anti‐B cell antibody. This study also supports the identity of the subset of cells responsible for antibodydependent and natural cell‐mediated cytotoxicit y and the similarity in their mechanisms.
Derivation of hybrids between a thymoma line and spleen cells activated in a mixed leukocyte reaction
Authors: Köhler G. , Lefkovits I. , Elliott B. , Coutinho A.
Published: February 2007

We have established 16 independent hybrid lines derived from a fusion between an AKR thyrnoma and mixed leukocyte reaction‐stimulated C57BL/6 spleen cells. The hybrids express both parental H‐2 alleles and show hybrid glucose‐6‐phosphate isomerase activity. Two of the lines showed Fc receptor activity not expressed in the parental thymoma. The AKR Thy‐1.1 allele was expressed in all hybrid lines, but no Thy‐1.2 could be detected. No killing activity was retained in the hybrid cells, probably because Sendai virus‐mediated fusion of killer cells resulted in the lysis of the thymoma fusion partner.
Idiotype‐bearing and antigen‐binding receptors produced by blood T lymphocytes in a case of human myeloma
Authors: Preud'Homme J.L. , Klein M. , Labaume Sylvaine , Seligmann M.
Published: February 2007

Twenty‐five to 30 % of blood lymphocytes from a myeloma patient with an IgGl(k) protein with antibody activity to horse α2‐macroglobulin (α2M) reacted with purified IgG from a rabbit antiserum to the idiotypic determinants of this protein. A small proportion of these idiotype‐bearing lymphocytes were IgG‐bearing B cells, but most of them were T cells. Several experiments demonstrated the actual synthesis of the idiotypic structures carried by the T lymphocytes. All idiotype‐bearing lymphocytes bound horse α2M, and the structures that bore the idiotype and bound the antigen were shown to completely cocap. After biosynthetic labeling with 14C‐labeled amino acids, immunoprecipitation and sodium dodecyl sulfate gel electrophoresis, the anti‐idiotypic serum and the α2M antigen were found to react with the same molecules. Preliminary data on the size of these antigen‐binding T lymphocyte‐derived molecules are in accord with those of Binz and Wigzell (Scand. J. Immunol. 1976. 5: 559) in the rat. The finding in this patient with multiple myeloma of a homogeneous and possibly malignant population of T lymphocytes, synthesizing identical antigen receptors which share idiotypic (but not isotypic) determinants of the immunoglobulin molecule produced by the malignant B cell clone, therefore confirms in man the results of several recent studies in other mammalian species.
Idiotype‐specific neonatal suppression of phosphorylcholine‐responsive B cells
Authors: Accolla R. S. , Gearhart Patricia J. , Sigal N. H. , Cancro M. P. , Klinman N. R.
Published: February 2007

The effect of neonatal anti‐idiotypic suppression on the expression of B cells of the T15 clonotype has been investigated at the level of individual clonal precursor cells. The results indicate that B cells of the T15 clonotype are almost completely eliminated from the repertoire for four months after neonatal injection of allogeneic anti‐idiotypic serum. The degree of this suppression is dependent on the amount of anti‐idiotypic antibody administered and is less profound if anti‐idiotypic antibody is given after the first week of life. No suppression was observed when anti‐idiotypic antisera were administered to mice 30 days of age or older, which may indicate that immature B cells are the population most susceptible to suppression. However, since suppression could be reversed by administration of T15 myeloma protein several days after injection of anti‐idiotype, the inability to suppress adult BALB/c mice may have been due to the high level of T15 idiotype normally present in their serum. Finally, phosphorylcholine‐responsive B cells of identifiable clonotypes other than T15, even a clonotype sharing antigen‐combining site determinants with T15, appear unaffected by anti‐T15 suppression.
Evolution of the lymphoid system II. Evidence for immunoglobulin determinants on all rainbow trout lymphocytes and demonstration of mixed leukocyte reaction
Authors: Etlinger H. M. , Hodgins H. O. , Chiller J. M.
Published: February 2007

Indirect fluorescent antibody analyses utilizing antiserum specifc for rainbow trout serum immunoglobulin (Ig) demonstrated that essentially all rainbow trout lymphocytes from thymus, spleen, anterior kidney and peripheral blood possess either Ig determinants or structures which cross‐react with those determinants found on serum Ig.

Peripheral blood leukocytes from rainbow trout were found to be capable of participating in a mixed leukocyte reaction. This observation is discussed in terms of the evolution of T cell function.
Conformational flexibility of an antibody combining site composed of two identical V regions
Authors: Gavish M. , Dwek R. A. , Givol D.
Published: February 2007

The variable portion of the light chain (VL) of protein 315 was studied as a model for antibody composed of two “like” chains. VL exists as a dimer which contains the binding subsite for the dinitrophenyl (Dnp) ring of Dnp ligands. Circular dichroism analysis of hapten‐protein complex demonstrated that the geometry of the Dnp hapten in the (VL)2 binding site is different from that in the Fv (composed of VL–VH) site. The VL dimer was found to be present in two distinct, pH‐dependent conformations which differ markedly in their binding properties. At pH 8.0 VL dimer binds two Dnp‐lysine per dimer, whereas at pH 6.0 only one ligand is bound per (VL)2. The association constant of (VL)2 for Dnp‐L‐lysine at pH 6.0 is 3–4‐fold higher than that at pH 8.0. The geometry of the hapten in the combining site is also different in the two conformers of (VL)2 as can be judged from the disappearance at pH 6 of the 480 nm and 390 nm absorbance bands in the difference spectrum of VL‐bound Dnp‐caproate. The pH‐dependent changes in the difference spectra between bound and free ligands were used to follow the transition between the two conformers of VL dimer. It was concluded that the pKa of this transition is at pH 6.9. The change in VL conformation is also expressed in a 2–3‐fold enhancement of VL fluorescence between pH 6 and pH 8, suggesting that the conformation at pH 8 which binds two ligands is more open, whereas at pH 6 a more tight conformation exists, binding one ligand with higher affinity. Such changes were not observed with Fv which is composed of both VL and VH‐These data suggest that an antibody site composed of two like chains (VL–VL) can undergo marked conformational changes at physiological pH values. The relevance of this finding to problems of receptors on thymus‐derived lymphocytes is discussed.
Human B cell differentiation. I. Immunoglobulin synthesis induced by Nocardia mitogen
Authors: Lêthibichthuy  , Ciorbaru Rita , Brochier J.
Published: February 2007

Nocardia water‐soluble mitogen (NWSM) is a mitogen which activates human B lymphocytes even in the absence of T cells. Tonsil and peripheral blood lymphocytes cultured in the presence of NWSM gave rise to large numbers of cells containing cytoplasmic immunoglobulins of IgM, IgA or IgG classes. The number of plasma cells appeared to be elevated as early as day 3 of culture and peaked on day 5 or 7. The IgM response preceded the development of cells containing other Ig classes, and was found to remain predominant on days 5 and 7. A similar number of plasma cells were generated in T‐deprived suspensions; however, a quantitative regulation by T cells cannot yet be excluded. The response to pokeweed mitogen appeared to be similar, except that it was often less intense and not observed in the absence of T cells. Very few or no IgD‐containing cells were found to be differentiated with both mitogens.
Rapid disappearance from serum of intravenously injected rat myeloma IgA and its secretion into bile
Authors: Jackson G. D. F. , Lemaǐtre‐Coelho Isabel , Vaerman J.‐P. , Bazin H. , Beckers A.
Published: February 2007

Intravenously injected monoclonal rat IgA is first removed from rat serum at a very fast rate (93% in 4 h), then at a much slower rate (t/2 = 24 h). The rapid initial disappearance is thought to be due in part to secretion into rat bile. This was demonstrated by rat liver perfusions with semisynthetic medium containing diluted (1:200) IgA myeloma serum. During perfusion, the cannulated bile displayed increasingly high levels of this IgA, with a bile to medium ratio of 38 after 1 h of perfusion; at the same time, there was a 40% drop of the rat monoclonal IgA concentration in the medium, which was not observed for rat IgG2a and albumin. All of the monoclonal biliary IgA was bound to secretory component. The rat liver is thus able to actively secrete a monoclonal IgA from the circulation into bile against a strong concentration gradient.
Eosinophil‐dependent cytotoxicity in rat schistosomiasis. Involvement of IgG2a antibody and role of mast cells
Authors: Capron Monique , Capron A. , Torpier G. , Bazin H. , Bout D. , Joseph M.
Published: February 2007

Using Schistoma mansoni schistosomula collected in vitro and sensitized with 42‐day‐infected rat serum, normal rat peritoneal cells enriched in eosinophils were proven to subsequently adhere to and kill the schistosomula within 24 to 48 h. The cell‐dependent, heat‐stable antibody in infected rat serum reached a peak between 30 and 42 days after infection. Inhibition experiments with aggregated immunoglobulins indicated the role of IgG2a antibody in the adherence of eosinophils to sensitized schistosomula. The immune absorption technique showed that IgG2a antibody was involved in the mechanism of cytotoxicity of effector to target cells, whereas the role of IgE antibody could be excluded.

Ultrastructural studies revealed the constant presence of eosinophils and mast cells in contact with schistosomula. The use of purified cell populations showed that the cytotoxic effect of the original cell population was significantly decreased after depletion of mast cells and partially restored after addition of mast cells. These observations, together with those concerning the role of IgE immune complexes in macrophage cytotoxicity, suggest the possible participation of anaphylactic antibodies in immunity to schistosomes in the rat.
Suiciding of lymphocytic precursor cells by tritiated nucleosides, in vitro
Authors: Uyeki E. M. , Nishimura T. , Bisel Teresa U.
Published: February 2007

Differences in suiciding by various tritiated nucleosides were observed between two functional assays for in vitro lymphocytic precursor cell development, the hemolysin plaque‐forming cell (PFC) assay and the B lymphocytic colony‐forming cell (CFC‐L) assay, using BDF1 mouse spleen cells. PFC growth was markedly reduced by an early (days 0–1) pulse of tritiated deoxyadenosine ([3H]dAdo), but relatively unaffected by a pulse of tritiated thymidine ([3H]dThd) during the same interval. In contrast, CFC‐L formation significantly dropped after an early (day 0) [3H]dThd pulse, as well as after pulses of [3H]dAdo and the corresponding tritiated ribosides, uridine and adenosine. This implied a cycling state in an early lymphocytic precursor cell, as opposed to the PFC insensitivity to an early [3H]dThd pulse. The response pattern of colonies and clusters to [3H]dThd supported our notion of a delayed suiciding of CFC contributing to the increase in cluster numbers.
The role of complement factors in acute antibody‐mediated rejection of mouse skin allografts
Authors: Berden J. H. M. , Capel P. J. A. , Koene R. A. P.
Published: February 2007

Established, H‐2 incompatible, mouse skin allografts are destroyed in 24–48 h by a single intravenous injection of specific alloantibody and heterologous complement (C) from rabbits (RC), guinea pigs (GpC) or humans (HC). Mouse complement (MC) itself is inefficient in this respect since grafts are not destroyed by the injection of antibody alone. This is in keeping with the low efficiency of MC in in vitro cytolysis.

We have studied the role of different C factors in this model. Two patterns were observed. (a) Three C‐deficient sera (GpC‐R4, GpC‐R3, RC‐R6) showed neither activity in vitro (C‐mediated lymphocytotoxicity in a trypan blue assay) nor did they induce graft destruction. Activity in vitro and in vivo could be completely reconstituted with the appropriate C component. (b) Two C‐deficient sera (GpC‐R1 and HC‐R9) were inactive in in vitro cytotoxicity but, nevertheless, induced destruction of the skin grafts if injected with antibody. Thus, in vivo, the mouse seemed to provide the deficient factor, and this was confirmed by the observation that in vitro cytotoxicity could be reconstituted not only with the appropriate C component, but also with normal mouse serum. The results show that the inefficiency of MC in vitro and in vivo does not reside in the factors C1 or C9. Furthermore, in our model C is activated via the classical pathway, and at least exogenous C4, C3 and C6 are required to induce acute antibody‐mediated graft destruction.

From the experiments with C6‐deficient serum which has normal chemotactic properties, it is concluded that activation of chemotactic factors with attraction of granulocytes is not sufficient to induce rejection, but that the activation of the membrane attack unit is required.
Regulation of delayed‐type hypersensitivity. III. Effect of cyclophosphamide on the suppressor cells for delayed‐type hypersensitivity to sheep erythrocytes in mice
Authors: Gill H. K. , Liew F. Y.
Published: February 2007

A previous study (Eur. J. Immunol. 1977. 7: 714) has shown that mice injected intravenously (i.v.) with 1 × 109 sheep red blood cells (SRBC) produce cells which suppress delayed‐type hypersensitivity (DTH). These suppressor cells are Θ‐positive, antigen‐specific and act via a soluble factor which does not bear immunoglobulin determinants (Eur. J. Immunol. 1978. 8: 168). The present paper demonstrates that these suppressor cells are inhibitable by cyclophosphamide (CY). Mice injected with graded amounts of CY two days prior to SRBC injection, showed maximum augmentation of DTH at 200 mg/kg body weight, a dose which completely suppressed the appearance of splenic plaque‐forming cells (PFC) to SRBC. In contrast, lower doses of CY enhanced both DTH and PFC responses. Time course studies showed that CY inhibited the precursors of suppressor cells and had little or no effect on suppressor cells which have already encountered antigens. This was further confirmed by passive transfer studies which showed that suppressor cells were inhibited if CY was administered at the same time or 2 days before SRBC injection, but were not affected if CY was given after antigen stimulation. Direct evidence for the effect of CY on suppressor cells was obtained by cell fractionation with a Ficoll density gradient. The denser suppressor cell population was absent from the spleens of mice treated with 200 mg/kg of CY 2 days before i.v. injection with 1 × 109 SRBC.
Regulation of the mixed leukocyte culture reaction by suppressor cells
Authors: Rode H. N. , Uotila Marjatta , Gordon J.
Published: February 2007

Regulation of the mixed leukocyte culture (MLC) reaction by suppressor cells raised and tested in MLC has been evaluated. The experiments described suggest that suppressors are distinct from cytotoxic T lymphocytes (CTL), both in terms of conditions optimal for their activation, as well as through demonstration of efficient suppression in the total absence of cytotoxic activity. Suppressor cells inhibit the activation of the precursors of CTL, and may also prevent the production of the lymphokine blastogenic factor; they do not appear to interfere with the reaction of primed cells. It is suggested that suppressor cells may regulate the MLC reaction by preventing recruitment of fresh competent cells, and by limiting the duration of the reaction of cells already activated.
Studies on the nature of the cell surface antigen reacting with cytolytic T lymphocytes in murine oncornavirusinduced tumors
Authors: Gomard Elisabeth , Levy J. P. , Plata F. , Henin Yvette , Duprez Véronique , Bismuth A. , Reme T.
Published: February 2007

The nature of the target antigen, expressed on murine sarcoma virus (MSV) and related murine tumors which reacts with T killer lymphocytes, remains ill‐defined. The experiments reported here show that: (a) the previously described H‐2 restriction phenomenon is found under all experimental conditions including 3–4 and 16–20‐h chromium release tests. With 16–20 h tests and highly efficient T lymphocytes however, quantitative methods are necessary to demonstrate the H‐2 restriction. These results support the hypothesis that H‐2 molecules may be determinant in the structure and/or in the function of the cytolytic T lymphocyte (CTL) reactive antigen. (b) Under syngeneic conditions (i.e. using H‐2‐identical immune lymphocytes, stimulators and target cells), the pattern of specificities recognized by anti‐MSV or anti‐Friend T killer cells on 20 different lymphomas suggests that the main reactive antigen is an “FMR‐like” substance. Identical conclusions were drawn from competition experiments. (c) Blockings were obtained by pre‐incubation of the target cells with a goat anti‐gp70, suggesting a possible role of the viral gp70 in the antigen recognized. However, this could be due to nonspecific reactions as two other anti‐gp70 sera as well as with antisera directed against the viral components gp45, pr60, p30, p15, p12 and p10 did not block. The CTL/tumor cell interaction was not inhibited by virion‐associated antigens added to the medium. Lysostrip and co‐capping experiments have failed to reveal an association between H‐2 and gp70. The nature of the viral protein bearing the “FMR‐like” substance therefore remains to be established.
Cytofluorometric analysis of macrophages activated in vivo or in vitro
Authors: Stadler Beda M. , De Weck A. L.
Published: February 2007

The relative RNA content of single macrophages was measured by cytofluorometry after differential staining of cellular DNA and RNA with the metachromatic fluorescent dye acridine orange. This method allowed the differentiation of two major groups in the adherent macrophage population differing in their RNA content. After in vivo stimulation of mice (by injection of thioglycollate medium) or guinea pigs (by injection of oil), an increasing percentage of macrophages possessing a high RNA content is recovered. In vitro stimulation of macrophage cultures with lipopolysaccharide had the same enhancing effect on cellular RNA content. Cytofluorometric measurement of RNA content may possibly become an efficient and rapid method of measuring macrophage activation.
Primary in vitro antibody formation in the rat: partial characterization and properties of an inhibitor cell present in normal spleen
Authors: Corvalán J. R. F. , Howard J. C.
Published: February 2007

Rat spleen cells are shown to be unresponsive to sheep red cells (SRBC) in vitro under conditions in which thoracic duct lymphocytes (TDL) respond very well. By adding unresponsive spleen cells to responsive TDL cultures, the spleen cells are shown to contain an inhibitor capable of preventing the response to SRBC. The inhibitory activity is a property of live cells; it is sensitive to radiation doses as low as 100 R × rays and to mitomycin C. It can be completely removed from spleen cell suspensions by extraction with large amounts of carbonyl iron or by filtration through nylon wool columns. It is less efficiently removed by filtration through Sephadex G‐10 columns, and is completely resistant to the cytotoxic effects of silica. From a practical point of view, extraction of a spleen cell suspension with carbonyl iron is a useful method of obtaining fully responsive lymphocyte populations from rat spleen.
Ontogeny of B lymphocyte function. VI. Ontogeny of thymus cell capacity to facilitate the functional maturation of B lymphocytes
Authors: Szewczuk M. R. , Sherr D. H. , Siskind G. W.
Published: February 2007

The differentiation of the B cell population from fetal mice to produce a normal, adult‐like, heterogeneous response, with respect to antibody affinity, has been shown to require (or to be facilitated by) thymus cells. The maturation of the thymus cell population to be capable of facilitating this differentiation of the B cell population was studied. It was found that the thymus cell population acquires the capacity fo facilitate (or induce) this maturation of the B cell population between seven and ten days after birth. Thus, the normal maturation of the B cell population to give a response which is heterogeneous with respect to affinity, appears to be controlled by the maturation of thymus function.
Acquired heterophile antigens on the surface of human cell lines
Authors: Aguilera S. , Ivanyi J.
Published: February 2007

Chicken IgM antibodies raised against sheep erythrocytes (SE) reacted with a heterophile carbohydrate antigen designated as “HC”. This antigen was visualized by SE rosette formation with antibody‐sensitized and formaldehydefixed target cells. Cells from eight lymphoblastoid lines and ten lines of diverse histogenetic origin all expressed HC on their surface to a greater or lesser degree when grown in fetal calf serum (FCS). Lymphoblastoid cell lines, HSB2 and Namalva, lost most of their HC antigen after three cell divisions when grown in medium which contained normal human serum (NHS) instead of FCS. The acquired origin of HC was demonstrated by the conversion of HSB2‐HC+ into HSB2‐HC' cells after incubation in the presence of FCS or fetuin for 18 h at 37°C. The acquisition of HC antigen depended on the concentration of fetuin as well as the time and temperature of incubation. The presence of NHS in the culture medium reduced the degree of HC incorporation. The level of HC expressed on the cell surface was reduced by treating HSB2 cells with sodium periodate but not by proteolytic enzymes. Competitive inhibition with hog blood group substance and sheep IgG suggested similar specificity of HC on target cells which had been sensitized with either fetuin or sheep IgM (Eur. J. Immunol. 1977.7:204). The avidity of chicken antibodies t o HC h either of these systems was several orders of magnitude lower than the binding to SE.