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Biomedical subjects

B Benacerraf

Publications and source records attributed to B Benacerraf.

At least 343 records · Page 19Linked to original sources
PubMed1973

Cell interactions between histoincompatible T and B lymphocytes. II. Failure of physiologic cooperative interactions between T and B lymphocytes from allogeneic donor strains in humoral response to hapten-protein conjugates.

Several experimental approaches, designed specifically to circumvent the possible contribution of a complicating "allogeneic effect," have been successfully used to answer the question of physiologic cooperative interactions between histoincompatible T and B lymphocytes in antibody responses to hapten-protein conjugates. This was accomplished for in vivo cell transfer studies by using an F(1) hybrid host as the recipient of irradiated, carrier-primed T lymphocytes from one parent and 2,4-dinitrophenyl (DNP)-primed B lymphocytes from the opposite strain. Under these conditions, very good T-B cell cooperative interactions were observed to occur between T and B lymphocyte populations derived from syngeneic donors, whereas no cooperative response was obtained when T cells were derived from one parental strain and B cells from the other. Corroborative experiments were performed in a totally in vitro system in which DNP-primed B cells developed good secondary anti-DNP antibody responses in vitro to soluble DNP-keyhole limpet hemocyanin (KLH) when cultured in the presence of irradiated KLH-primed T cells derived from syngenic donors but not from allogeneic donors. The failure of histoincompatible T and B lymphocytes to effect physiologic cooperative interactions has important implications for our understanding of how such interactions normally occur. The possibility that these results reflect the existence of a "block" of some sort to cell-cell interaction by virtue of the presence of a foreign major histocompatibility antigen on the surface of either cell has been definitively ruled out in the present studies. These observations demonstrate that the gene(s) that conditions the capability for physiologic T-B cell cooperation must be shared in common by the respective cell types, and suggest, furthermore, that this gene (or genes) belongs to the major histocompatibility system of the mouse. These findings, together with other relevant phenomena described previously, have led us to postulate that there exists on the B lymphocyte surface an "acceptor" molecule either for the putative active T cell product or for the T cell itself. The important genetic considerations and the possible sequence of events surrounding the actual T-B cell interaction implied by these postulates are discussed in detail.

Animals↗
PubMed1973

Induction of immunological tolerance in bone marrow-derived lymphocytes of the IgE antibody class.

Administration of the 2,4-dinitrophenyl (Dnp) determinant conjugated to the "nonimmunogenic" copolymer of D-glutamic acid and D-lysine (D-GL) induces Dnp-specific immunological tolerance which is essentially restricted to bone marrow-derived (B) lymphocytes. Previous studies have demonstrated tolerance induction by Dnp-D-GL in predominantly B lymphocytes of the IgG class. The present studies establish and analyze conditions for tolerance induction in Dnp-specific B lymphocytes of the IgE antibody class by taking advantage of: (i) the relatively easy capacity to induce tolerance with Dnp-D-GL in an animal or cell population previously primed to the Dnp determinant; (ii) previously established parameters for the successful adoptive transfer of Dnp-specific IgE antibody responses; and (iii) the capacity to induce, and maintain a state of Dnp-specific tolerance with Dnp-D-GL in adoptive transfer responses. Using these approaches, we have successfully rendered Dnp-specific B cells of the IgE class profoundly and apparently irreversibly tolerant after exposure of such cells to Dnp-D-GL. These observations represent a starting point of wide potential for solving many therapeutic problems concerned with clinical allergies.

Animals↗
PubMed1973

Purification of Hodgkin's disease tumor-associated antigens.

Two antigens that exist in high frequency in tumor tissues of patients with Hodgkin's disease have been obtained in relatively concentrated form. Extracts of Hodgkin's spleen tumor tissue, when subjected to chromatography on Sephadex G-200, separate into three major protein peaks of which only the first (peak I) possesses the predominant antigenic activities associated with the disease. Antigenic analysis performed with hyperimmune rabbit antisera obtained after repeated immunizations with peak I proteins demonstrated that this fraction contained both F and S antigens associated with Hodgkin's disease and small contaminant amounts of an antigen associated with normal lymphocytes. The tissue distribution patterns of the Hodgkin's disease tumor-associated antigens suggest that they both originate in lymphoid tissues and that the F antigen may represent a product of reactive lymphocytes while the S antigen may be a dedifferentiation antigen expressed in very immature lymphocytes.

Animals↗
PubMed1973

Cell interactions between histoincompatible T and B lymphocytes. The H-2 gene complex determines successful physiologic lymphocyte interactions.

We used congenic-resistant mouse strains to answer questions concerning the respective roles of genes coding for major histocompatibility and background genotypes in T (thymus-derived)-B (bone marrow-derived) lymphocyte cooperative responses to hapten-protein conjugates. These studies demonstrate conclusively that the gene or genes present in the H-2 complex control the capacity of antigen-specific T and B cells to effectively interact. These findings led us to postulate that there exists on the B-lymphocyte surface an "acceptor" molecule for the active T-cell product or for the T cell itself.

Animals↗
PubMed1973

Immunologic events in experimental hypersensitivity granulomas.

Polyacrylamide beads were covalently linked to proteins and injected intravenously into normal or immune guinea pigs. The beads trapped in the lung produced very mild foreign body granulomas in nonimmune guinea pigs. In immune guinea pigs, severe granulomas developed which progressed through the several characteristic histologic stages with time. Severe granulomatous reactions developed only upon recognition of carrier determinants of hapten-protein conjugates; thus guinea pigs immune to dinitrophenyl hapten (DNP)-hemocyanin developed characteristic granulomas only upon injection of beads coated with hemocyanin or DNP-hemocyanin, but not with DNP on another unrelated antigen. Granulomatous reactivity was passively transferred into normal animals by lymph node cells but not by serum antibody from sensitized guinea pigs.

Acrylamides↗
PubMed1972

Immunological tolerance in bone marrow-derived lymphocytes. I. Evidence for an intracellular mechanism of inactivation of hapten-specific precursors of antibody-forming cells.

Administration of the 2,4-dinitrophenyl (DNP) derivative of the copolymer of D-glutamic acid and D-lysine (D-GL) to inbred mice induces a state of DNP-specific tolerance in such animals irrespective of their immune status at the time of treatment. Taking advantage of the relative ease with which DNP-D-GL can induce tolerance in an animal previously primed with an immunogenic DNP-carrier conjugate, we have established conditions for tolerance induction in an adoptive cell transfer system. Thus, the adoptive secondary anti-DNP antibody response of DNP-keyhole limpet hemocyanin (KLH)-primed spleen cells was completely, or almost completely, abolished by exposure of such cells to DMP-D-GL either in vivo or in vitro. Tolerance induction in vivo occurred irrespective of whether the DNP-primed cells were exposed to DNP-D-GL in the donor animal before adoptive transfer or in recipient mice after transfer. In the latter situation, it was possible to show that tolerance induction in this model occurs very rapidly (1 hr) and with relatively low doses of tolerogen (50 microg). Incubation of DNP-KLH-primed cells with DNP-D-GL in vitro under varying culture conditions also resulted in depression of the adoptive secondary response of such cells, although the kinetics and degree of tolerance induction in this way were slightly different from that obtained by in vivo tolerization. Utilizing the adoptive transfer tolerance system, it was possible to approach certain questions concerning the mechanism of tolerance induction and fate of tolerant bone marrow-derived (B) lymphocytes in the DNP-D-GL model. The possibility that suppression of anti-DNP antibody from the DNP-D-GL reflects blocking of surface receptor molecules on B lymphocytes has been ruled out by several experimental observations. The most conclusive evidence on this point derives from the failure of enzymatic treatment with trypsin to reverse the tolerant state induced by in vitro exposure of primed cells to DNP-D-GL, whereas trypsinization completely restored the immunocompetence of DNP-KLH-primed cells rendered unresponsive by exposure to DNP-ovalbumin in vitro. The present studies also demonstrate that the tolerant state induced by DNP-D-GL represents a predominantly irreversible inactivation of specific B lymphocytes. This conclusion is derived from experiments in which it was found that tolerance was maintained through as many as two serial adoptive transfers performed over a period of time of at least 24 days from the single exposure of such cells to the tolerogen. Moreover, the possibility that maintenance of tolerance through such serial transfers was due to inadvertent transfer of tolerogenic doses of DNP-D-GL was definitively ruled out. It appears, therefore, that DNP-specific tolerance induced by DNP-D-GL is an example of irreversible inhibition of cell reactivity to antigen reflecting yet-to-be-determined events at the intra- and subcellular levels.

Animals↗
PubMed1972

Genetic factors controlling anti-sheep erythrocyte antibody response and immunoglobulin synthesis in backcross and F2 progeny of mice genetically selected for "high" or "low" antibody synthesis.

Agglutinin responses to sheep erythrocytes and immunoglobulin heavy chain phenotypes determined in F(1), F(2), and backcross progeny of mice genetically selected for high and low antibody synthesis indicated that an immune response gene for sheep erythrocytes is linked to the immunoglobulin heavy chain allotype. Mice homozygous for the phenotype of the high line had significantly higher titers than mice homozygous for the phenotype of the low line. An association was also observed in some progeny of the backcross of the F(1) generation with the low line. However, the control of the immune response was clearly multigenic since heterozygous mice of the same phenotype (2/3, 5) resulting from the two backcrosses (high and low) had very different immune responses. Immunoglobulin levels in the same progeny showed no linkage to the immunoglobulin allotype but a rather simple pattern of inheritance.

Animals↗