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Biomedical subjects

B Benacerraf

Publications and source records attributed to B Benacerraf.

At least 415 records · Page 23Linked to original sources
PubMed1968

Specificity of cellular immune responses. Antigen concentration dependence of stimulation of DNA synthesis in vitro by specifically sensitized cells, as an expression of the binding characteristics of cellular antibody.

In vitro antigen stimulation of DNA synthesis in lymph node cultures from immunized guinea pigs can be obtained with very low (10(-4) microg/ml) antigen concentrations in the culture fluid. Immunization with low doses of DNP-GPA leads to a cell population capable of being stimulated, on the average, by low concentration of antigen whereas immunization with large antigen doses results in a sensitive cell population requiring, on the average, high antigen concentrations for stimulation. These findings correlate well with the affinity for hapten of the serum antibodies produced by these guinea pigs. Both delayed reactions in vivo and DNA synthesis in vitro can be stimulated by hapten conjugated to proteins different from that used in primary immunization. However the immunizing conjugate is much more effective in terms of antigen concentration required for a given response. These results can be understood in terms of a thermodynamically driven interaction of antigen (or "processed" antigen) with cell-associated antibody.

Adjuvants, Immunologic↗
PubMed1968

Hapten carrier relationships in the DNP-PLL foreign albumin complex system: induction of tolerance and stimulation of cells in vitro.

Genetic nonresponder guinea pigs made tolerant to BSA and then immunized with DNP-PLL.BSA failed to make anti-DNP-PLL antibodies. Thus, tolerance to a carrier protein renders animals unresponsive to the hapten which it bears. The addition in vitro of DNP-PLL or DNP-GL to lymph node cell cultures derived from genetic responder animals immunized with these materials led to a significant stimulation of (3)H-thymidine incorporation into DNA. However, the addition of DNP-PLL or DNP-GL to lymph node cell cultures from nonresponder animals immunized with these materials failed to produce any stimulation of DNA synthesis. Furthermore, the addition of DNP-PLL to lymph node cell cultures from nonresponder animals immunized with DNP-PLL.BSA or DNP-PLL.OVA also failed to stimulate cell proliferation in spite of the fact that the lymph node cells of these animals were producing anti-DNP-PLL antibodies. The above facts suggest that the function of the PLL gene product is to act at an early crucial step in the immune mechanism to form an antigen-inducer complex. The specificity of this early step may be of a simple order and different than that of the antibody which is later produced in the immune response.

Animals↗
PubMed1967

A study of the passive transfer of delayed hypersensitivity to DNP-poly-L-lysine and DNP-GL in responder and nonresponder guinea pigs.

A study of the passive transfer of delayed hypersensitivity to DNP-poly-L-lysine and to DNP-GL was performed in Hartley guinea pigs. Delayed hypersensitivity to DNP-PLL and DNP-GL could be transferred successfully only by means of sensitized cells from genetic responder guinea pigs and in most cases, only into those guinea pigs genetically capable of responding to PLL. The inability to transfer delayed hypersensitivity to DNP-PLL or DNP-GL to genetic nonresponder guinea pigs is not the result of the early destruction of the transferred cells by an incompatible host, since it was shown that delayed hypersensitivity to ovalbumin could be successfully transferred from guinea pigs with the PLL gene into genetic nonresponder animals. The requirement of active participation of specific and genetically controlled host mechanisms in the successful passive transfer of delayed sensitivity to DNP-PLL and DNP-GL has been demonstrated.

Animals↗
PubMed1967

Antihapten antibody specificity and L chain type.

Two types of light polypeptide chain (kappa and lambda) are present in guinea pig immunoglobulins. The ratios of K/L molecules in anti-hapten antibodies differ sometimes markedly from that found in normal serum. Anti-DNP antibodies and anti-pipsyl antibodies have, respectively, a higher and a lower than normal K/L ratio. The possibility that the L chain type affects the range of configurations which the antibody-combining site may assume was investigated. Fractional precipitation of anti-DNP antibodies from serum of guinea pigs immunized with DNP(44)-BSA was performed using limiting amounts of antigen. Antibody fractions were purified from each precipitate, their affinities for epsilon-DNP-L-lysine measured by fluorescence quenching (K(0)) and the K/L ratio estimated by precipitation with specific antisera. Increasing concentrations of L molecules were found in fractions with decreasing K(0). In other experiments, fractional precipitation and purification of antibodies which cross-react with DNP was performed in serum of animals immunized with pipsyl-BGG. The K/L ratio in antibodies isolated from these fractions was much higher than in fractions which do not cross-react with DNP. These results show that K molecules are better adapted to react with the DNP hapten than L molecules. The K/L ratio in anti-DNP antibody was shown to increase in the course of immunization, at the same time that the K(0) is increasing. This rise in K(0) is markedly delayed when larger doses of antigen are employed.

Animals↗
PubMed1967

Specificity of the antibodies produced by single cells following immunization with antigens bearing two types of antigenic determinants.

A combination of double immunofluorescent technique and radioautographic localization of radioactive antigens was used to investigate the question whether single antibody-producing cells can make antibodies of more than one specificity after immunization with antigens bearing more than one determinant. When guinea pig gamma(2)-globulins, containing the F(ab')(2) and Fc determinants, were used to immunize rabbits, a small percentage of cells (3.7%) were stained with both the anti-F(ab')(2) and anti-Fc reagents. These results were shown to be due to the lack of absolute specificity of the detecting antigen and antibody reagents which can be obtained for use in this system. However, when immunological systems such as hapten-protein conjugates were used, and where completely specific antigen and antibody reagents could be prepared, the results were unequivocal. The individual lymph node cells from rabbits or guinea pigs immunized with hapten-protein conjugates produced antibodies against the hapten or antibodies against the antigenic determinants of the carrier molecule, never antibodies against both specificities.

Animals↗
PubMed1967

Cellular localization of anti-DNP-PLL and anticonveyor albumin antibodies in genetic nonresponder guinea pigs immunized with DNP-PLL albumin complexes.

Genetic nonresponder guinea pigs incapable of an immune response to DNP-PLL alone were immunized with DNP-PLL complexed to ovalbumin or bovine serum albumin. Under these circumstances the animals produce both anti-DNP-PLL antibodies and antibodies directed against the conveyor albumin. Thus immune response to DNP-PLL complexed to conveyor albumin molecules can serve as a simple model of hapten-carrier relationships. To explore these relationships the question whether these two types of antibody are synthesized by the same or by different plasma cells was investigated by a combination of a double immunofluorescent technique and radioautographic localization of radioactive antigen. It was shown that the anti-DNP-PLL antibodies and the antibodies against the carrier albumin molecule were produced in separate cells. No cell-producing antibodies with both specificities were detected out of 526 cells studied.

Animals↗