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Biomedical subjects

B Benacerraf

Publications and source records attributed to B Benacerraf.

At least 397 records · Page 22Linked to original sources

Linkage between the poly-L-lysine gene and the locus controlling the major histocompatibility antigens in strain 2 guinea pigs.

The data presented demonstrate linkage between the major histocompatibility locus of inbred strain 2 guinea pigs and a "specific immune response gene," the PLL gene, which controls responsiveness to poly-L-lysine and hapten conjugates of this polypeptide in these animals. This finding extends to another species and to a different immune system the linkage observed in mice between the H(2) locus and specific immune response genes at the Ir-1 locus. The general significance of the linkage of specific immune response genes to histocompatibility loci is discussed.

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Genetic control of the immune response of guinea pigs to limiting doses of bovine serum albumin: relationship to the poly-L-lysine gene.

The response of strain 2 guinea pigs to limiting doses of bovine serum albumin is under dominant genetic control linked with the poly-L-lysine gene. Inbred strains 2 and 13 guinea pigs make similar antibody responses to 10 mug bovine serum albumin, whereas strain 2 but not strain 13 animals produce significant amounts of antibodies in response to 0.1 mug. The relationship between the presence of the poly-L-lysine gene and the ability to respond to limiting doses of bovine serum albumin has also been investigated in random-bred Hartley strain guinea pigs.

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Immune response in vitro: independence of "activated" lymphoid cells.

Antibody formation against sheep erythrocytes by mouse spleen cells in vitro requires interactions among antigen-treated macrophages and lymphoid cells in cell culsters for only a finite time. During this critical period of interaction, lymphoid cells become "activated" and thereafter can develop into antibody-producing cells independently of native antigen, macrophages, and cell clusters.

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Transfer of responsiveness to hapten conjugates of poly-L-lysine and of a copolymer of L-glutamic acid and L-lysine to lethally irradiated nonresponder guinea pigs by bone marrow or lymph node and spleen cells from responder guinea pigs.

Hartley guinea pigs genetically unresponsive to hapten-PLL (poly-L-lysine) conjugates were lethally irradiated and given allogeneic bone marrow from Hartley responder animals. Many of the animals died of graft versus host disease before their response to 2,4-dinitrophenyl-PLL (DNP-PLL) could be measured. The immune response of the surviving recipient animals was evaluated by anti-DNP antibody production, development of delayed hypersensitivity to DNP-poly-L-lysine, as well as by lymph node cell stimulation in vitro by this antigen. 12 of 14 recipient animals thus treated made an immune response as measured by 2 of the 3 parameters. Strain 13 guinea pigs, genetically unable to respond immunologically to DNP-PLL and to DNP-GL (2,4-dinitrophenyl-L-glutamic acid L-lysine copolymer) were lethally irradiated and given bone marrow from (2 x 13) F(1) responder animals or strain 13 bone marrow and (2 x 13) F(1) lymph node and spleen cells. A high proportion of the animals survived this procedure; no evidence of graft versus host disease was observed. Three of three strain 13 animals irradiated and, given strain 13 bone marrow and (2 x 13) F(1) lymph node and spleen, and then immunized with DNP-PL, made a specific immune response. 7 of 10 irradiated strain 13 animals given strain 13 bone marrow and (2 x 13) F(1) lymph node and spleen made an immune response to DNP-GL. However, only one of six irradiated strain 13 animals made a vigorous immune response to DNP-GL after reconstitution with (2 x 13) F(1) bone marrow alone. The ability to transfer the immune response to PLL antigens from responder to nonresponder animals demonstrates unequivocally that the defect in the non-responder animals is immunological rather than due to some other type of non-immunological mechanism. The bone marrow contains all the immunological cells necessary for the expression of the PLL gene. However, the finding that (2 x 13) F(1) lymph node and spleen cells were more effective than (2 x 13)F(1) bone marrow cell populations (known to be a rich source of monocyte precursors) suggests that the cells in which the PLL gene function is expressed may be lymphocytes rather than monocytes and macrophages.

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The anamnestic antibody response to type 3 specific pneumococcal polysaccharide.

Rabbits immunized with killed type III pneumococci respond to anamnestic challenge by type specific polysaccharide (S III) with the synthesis of anti-S III antibody if a long interval is allowed to elapse between primary and secondary immunization. A study of the anti-S III antibody produced early and late in the immune response revealed no change in molecular class, banding pattern of dissociated light chains, or S III binding characteristics as measured under equilibrium conditions or by study of dissociation kinetics utilizing radioiodinated p-OH-benzyl-S III. Sequential booster injections of S III into rabbits primarily immunized with whole organisms 8 or 9 months earlier led to a progressive decrease in the number of animals showing successful anamnestic responses and in the magnitude of those responses. It is concluded that S III depletes the antigen sensitive cell population in the secondary response largely because of its limited ability to stimulate sustained proliferation by such cells.

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A quantitative study of the stimulation of DNA synthesis in lymph node cell cultures by anti-lymphocyte serum, anti-gamma globulin serum, specific antigen, and phytohemagglutinin.

Rabbit anti-guinea pig lymphocyte serum is an efficient stimulus of the synthesis of DNA by guinea pig lymph node cells in vitro. The ability of ALS to stimulate lymphocytes is characterized by its lack of dependence on prior sensitization, the magnitude of the response it elicits, and the stimulation of all sensitive lymph node cells simultaneously within a very narrow range of ALS concentrations. In contrast to this homogeneous response to ALS, the stimulation of lymph node cells by antigen proceeds in graded fashion over a wide range of concentrations, thus reflecting the heterogeneity of the response of sensitized cells to antigen. PHA gives a response which is intermediate between that of ALS and antigen. ALS appears to have specificity for membrane determinants shared by lymphocytes but not found on other tissues. This specificity does not involve cell-bound gamma globulin. The serum activity mediating lymphocyte stimulation as well as cytotoxicity is readily removed by absorption with lymph node cells.

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Genetic control of immunological responsiveness in guinea pigs to 2,4-dinitrophenyl conjugates of poly-L-arginine, protamine, and poly-L-ornithine.

The ability of guinea pigs to respond immunologically to dinitrophenyl (DNP)-poly-L-arginine, DNP-protamine, DNP polyornithine, and to unsubstituted poly-L-arginine and protamine is linked to the presence of the poly-L-lysine gene. This gene has previously been demonstrated to control the immune response of guinea pigs to poly-L-lysine, to a copolymer of L-glutamic acid and L-lysine and to haptenic derivatives of these materials. Although the ability to respond to each of these highly charged compounds is linked to the presence of the poly-L-lysine gene, the cellular immune responses to these antigens is highly individually specific.

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