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Biomedical subjects

B Benacerraf

Publications and source records attributed to B Benacerraf.

At least 361 records · Page 20Linked to original sources
PubMed1972

Hapten-specific tolerance. Preferential depression of the high affinity antibody response.

The induction of tolerance in guinea pigs with a 2,4-dinitrophenyl (DNP) derivative of a copolymer of copolymer of D-glutamic acid and D-lysine (D-GL) leads to a preferential depression of the capacity to produce high affinity anti-DNP antibody in response to immunization with DNP-guinea pig albumin. Thus, immunization 2 wk after tolerance induction with 3 mg of DNP-D-GL results in an immune response in which individual plaque-forming cells (PFC) secreting high affinity anti-DNP antibody are absent and in which the affinity of circulating anti-DNP antibody is reduced. A similar, but less marked, suppression is seen when 0.3 mg of DNP-D-GL is used for tolerance induction. If immunization is delayed until 2 months after tolerance induction, then suppression is restricted to the highest avidity PFC group. Our data is consistent with a state of tolerance in the pool of precursors of anti-DNP antibody-secreting cells induced as a result of their interaction with DNP-D-GL in the absence of specific "helper" cells, which appear to be lacking for DNP-D-GL. In such a situation, the affinity of receptors on precursor cells for tolerogen and the concentration of tolerogen appear to be crucial determinants of whether an individual cell will become tolerant.

Animals↗
PubMed1972

Antigen binding and capping by lymphocytes of genetic nonresponder mice.

Radioautographic study of the binding of GAT-(125)I to spleen cells of genetic responder and nonresponder mice demonstrates that among mice not injected with antigen all strains have approximately the same number of antigen-binding cells; after injection with antigen the number of antigen-binding cells increases in responders but not in nonresponders. Nonresponders are shown to make antibody after injection with GAT complexed with an immunogenic carrier, demonstrating the presence of potentially functional B cells in responders and nonresponders alike. When incubated in the warm, antigen-binding cells of both responders and nonresponders concentrate antigen at one pole of the cell, forming caps.

Animals↗
PubMed1972

Genetic control of thymus-derived cell function. I. In vitro DNA synthetic response of normal mouse spleen cells stimulated by the mitogens concanavalin A and phytohemagglutinin.

Concanavalin A- or phytohemagglutinin-stimulated DNA synthetic responses of 1 million normal mouse spleen cells in vitro were significantly different among various inbred strains. BALB/cJ (H-2(d)) responded better than C57BL/6J (H-2(b)) spleen cells, and the responses of C3H/HeJ or AKR/J (both H-2(k)) cells were intermediate. These responses, measured as the increment in thymidine-(3)H incorporation of mitogen-stimulated compared with unstimulated cultures, varied according to the number of cells cultured or the mitogen concentration. BALB/c spleens had the highest proportion of theta-positive cells, but no direct relationship between the proportion of theta-positive cells and the DNA synthetic response was observed. (BALB/cJ x C57BL/6)F(1) spleen cells responsed as well as BALB/c cells. Responses of spleen cells from (F(1) x C57BL/6) backcross littermates varied over a range equal to, or greater than, that of BALB/c and C57BL/6 cells. There was no correlation between H-2 specificity (H-2(bd) or H-2(bb)) or sex and the mitogen-stimulated DNA synthetic response of backcross animals. Con A- and PHA-stimulated responses of individual backcross animals were positively correlated with the level of thymidine-(8)H incorporation by unstimulated spleen cells. These results are consistent with autosomal dominant, non-H-2-linked, polygenic control of the mitogen-stimulated in vitro DNA synthetic response of mouse spleen cells.

Animals↗
PubMed1972

Radioresistance of carrier-specific helper thymus-derived lymphocytes in mice.

The effect of x-irradiation on the capacity of carrier-specific mouse T (thymus-derived) lymphocytes to exert a helper function for hapten-specific B (bone marrow-derived) lymphocytes in vivo has been investigated again. Helper function is abolished by exposure of such cells to x-irradiation before, or immediately after, transfer to adoptive hosts. On the other hand, when exposure to x-irradiation occurs under circumstances in which the carrier-primed cells are well-localized in the appropriate lymphoid organs, i.e., either in the carrier-primed animal or 24 hr after adoptive transfer to syngeneic recipients, the capacity of T lymphocytes to serve as specific helper cells is clearly radioresistant. Evidence indicates that x-irradiation results in undefined, and subtle, changes in the migratory capacity of mouse T lymphocytes, but not in abrogation of T-cell helper function.

Animals↗
PubMed1972

Specific immune response genes of the guinea pig. V. Influence of the GA and GT immune response genes on the specificity of cellular and humoral immune responses to a terpolymer of L-glutamic acid, L-alanine, and L-tyrosine.

The ability of guinea pigs to make immune responses to the random linear copolymer of L-glutamic acid and L-alanine, GA, and to L-glutamic acid and L-tyrosine, GT, is each controlled by a different immune response gene. On the other hand, the random linear terpolymer of L-glutamic acid, L-alanine, and L-tyrosine, GAT, which contains both GA and GT antigenic determinants, is immunogenic in all guinea pigs. After GAT immunization, all animals develop delayed hvpersensitivity and serum antibody specific for GAT. However, only those guinea pigs possessing the GA immune response gene demonstrate cross-reactive delayed hypersensitivity when challenged with GA. In addition, the anti-GAT antisera produced by those animals having the GA gene contain cross-reacting anti-GA antibodies. The sera from guinea pigs lacking the GA gene have no anti-GA antibody activity. Thus, we have demonstrated that a specific immune response gene controlling responsiveness to a "simple" antigen can determine the specificity of both cellular and humoral immune responses to a more complex antigen.

Alanine↗
PubMed1971

Specific immune response genes of the guinea pig. 3. Linkage of the GA and GT immune response genes to histocompatibility genotypes in inbred guinea pigs.

The ability of guinea pigs to form immune responses specific for each of the random copolymers, L-glutamic acid and L-alanine (GA) and L-glutamic acid and L-tyrosine (GT), is under the control of distinct autosomal dominant genes. By testing for the ability to respond to these copolymers among the progeny from the reciprocal backcross mating of responder (2 x 13)F(1) animals with the appropriate nonresponder parental strain, we have demonstrated that different unigenic autosomal dominant traits control the ability to respond to GA and GT respectively. The data further shows that the GA gene is linked to the poly-L-lysine (PLL) gene and to the locus determining the major strain 2 histocompatibility specificities and that the GT gene is linked to the locus controlling the expression of major strain 13 histocompatibility specificities. Analysis of the inheritance of the GT and PLL genes among the offspring from a mating of responder (2 x 13)F(1) guinea pigs with random-bred guinea pigs unable to respond to GT or PLL demonstrate that these genes segregate away from each other. Thus, the PLL gene and the genes to which it is linked, the GA gene and the major strain 2 histocompatibility locus, behave as alleles or pseudoalleles to the GT gene and the major strain 13 histocompatibility locus.

Alanine↗
PubMed1971

Histocompatibility specificity.

The lymph node cells from all L-glutamic acid and L-tyrosine (GT) responder random-bred guinea pigs were susceptible to lysis by strain 2 anti-strain 13 isoantisera in the presence of complement. These same antisera were cytolytic for lymph node cells of only some of the GT nonresponder animals. However, after absorption with cells, from a nonresponder guinea pig, susceptible to lysis, the anti-strain 13 antisera were no longer able to lyse cells from any GT nonresponder guinea pigs while retaining a large measure of their cytolytic activity for cells of all GT responder guinea pigs. Thus, at least two major strain 13 histocompatibility specificities are expressed on the cells of random-bred guinea pigs. The genetic locus controlling the expression of only one of those strain 13 histocompatibility specificities is linked to the GT immune response gene.

Animals↗
PubMed1971

Specific immune response genes of the guinea pig. I. Dominant genetic control of immune responsiveness to copolymers of L-glutamic acid and L-alanine and L-glutamic acid and L-tyrosine.

The immunogenicity of three random copolymers of amino acids with L-glutamic acid and L-alanine (GA), L-glutamic acid and L-tyrosine (GT), or L-glutamic acid, L-alanine, and L-tyrosine (GAT), administered in complete Freund's adjuvant, was studied in several inbred and random-bred guinea pig strains. The animals were tested for delayed sensitivity and their sera were assayed for the presence of antibody directed against the immunizing polymer. All of the guinea pigs developing delayed hypersensitivity also had significant antibody levels in their sera. Inbred strain 2 guinea pigs responded to immunization with GA, but failed to form detectable responses to GT. Inbred strain 13 animals, on the other hand, responded to GT, but not to GA. The (2 x 13)F(1) hybrids responded to both GA and GT with both delayed hypersensitivity and circulating antibody. Thus, the ability of these inbred guinea pigs to respond immunologically to GA or GT is controlled by distinct autosomal dominant genes. A variable percentage of random-bred guinea pigs, depending on their source as well as their strain, responded to immunization with GA and with GT. All guinea pigs, both inbred and random bred, responded to immunization with GAT. The ability to respond immunologically to GAT, therefore, does not seem to be under simple genetic control. However, the levels of anti-GAT antibody found in the sera of animals lacking the ability to respond to GA were much lower than those detected in GA responder animals.

Alanine↗
PubMed1971

Specific immune response genes of the guinea pig. II. Relationship between the poly-L-lysine gene and the genes controlling immune responsiveness to copolymers of L-glutamic acid and L-alanine and L-glutamic acid and L-tyrosine in random-bred Hartley guinea pigs.

The ability of guinea pigs to make immune responses to GA, a linear random copolymer of L-glutamic acid and L-alanine, GT, a random linear copolymer of L-glutamic acid and L-tyrosine, and PLL, a linear homopolymer of L-lysine, is controlled by different autosomal dominant genes specific for each of those polymers. We have investigated the relationship between the PLL gene and the GA and GT immune response genes by simultaneously immunizing random-bred Hartley strain guinea pigs with GA and PLL, GT and PLL, or GA and GT. In most Hartley guinea pigs the ability to respond immunologically to GA and to PLL is inherited together; that is, most animals responding to GA respond to PLL and vice versa. However, a few animals respond to either GA or to PLL but not both, demonstrating that the GA and PLL immune response genes are not identical but linked in most Hartley animals. Conversely, when simultaneously immunized with GT and PLL, most Hartley guinea pigs respond to either PLL or GT but not both, indicating that GT and PLL responsiveness tends to segregate away from each other. Thus, the GT and PLL immune response genes also are not inherited independently but, rather, behave as alleles or pseudoalleles. Similar results are observed when Hartley guinea pigs are simultaneously immunized with GA and GT. The ability to respond to GA segregates away from the ability to respond to GT. Our studies demonstrated that the specific immune response genes thus far identified in guinea pigs controlling the ability to respond to GA, GT, and PLL, respectively, are found on the same chromosome. In most Hartley animals, the GA and PLL immune response genes are often linked, i.e. occur on the same chromosome strand, and tend to behave as alleles or pseudoalleles to the GT immune response gene.

Alanine↗
PubMed1971

Carrier function in anti-hapten antibody responses. IV. Experimental conditions for the induction of hapten-specific tolerance or for the stimulation of anti-hapten anamnestic responses by "nonimmunogenic" hapten-polypeptide conjugates.

Administration of nonimmunogenic 2,4-dinitrophenyl (DNP) conjugates of copolymers of D or L-glutamic acid and lysine (GL) induces hapten-specific tolerance in nonimmune and DNP-ovalbumin-primed strain 13 guinea pigs. This tolerant state is evidenced by depressed anti-DNP antibody synthesis in response to challenge with DNP-ovalbumin and by a diminished frequency of DNP-specific antigen-binding cells and of anti-DNP antibody-secreting cells. Such a nonimmunogenic compound (DNP-D-GL) will nevertheless elicit a DNP-specific anamnestic antibody response when administered at an appropriate time to DNP-ovalbumin-primed guinea pigs undergoing a graft-versus-host reaction. These experiments are discussed in terms of a two-cell theory of stimulation of antibody responses.

Animals↗
PubMed1971

Carrier function in anti-hapten antibody responses. 3. Stimulation of antibody synthesis and facilitation of hapten-specific secondary antibody responses by graft-versus-host reactions.

The studies reported here demonstrate that immunocompetent lymphoid cells from allogeneic donor guinea pigs stimulate the synthesis of anti-DNP and anti-OVA antibodies by recipients previously primed with DNP-OVA. This allogeneic effect occurs spontaneously in the absence of any further anti-genic challenge. Furthermore, the transfer of allogeneic cells prepares DNP-OVA-primed recipients for a striking secondary anti-DNP response to DNP-BGG; this occurs in equal degree whether or not the cells are derived from BGG-primed donors. We suggest that the allogeneic cells function by virtue of a specific immunologic attack of grafted cells on host cells. This conclusion is made on the basis of the following evidence: (a) The failure of observing the phenomenon with L(2)C leukemia cells and irradiated strain 2 lymph node and spleen cells which, although capable of initiating a host-versus-graft response, are incapable of mediating graft-versus-host reactions; and (b) the inability of (strain 2 x strain 13) F(1) hybrids to mediate the allogeneic effect in strain 13 recipients. The analysis of this phenomenon may offer a key to the delineation of mechanisms involved in the activation of precursors of antibody-forming cells.

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