Antibody production in mice. VI. Effect of anti-carrier antibody on cellular co-operation in the primary anti-hapten antibody response.

We studied the effect of passively administered anti-carrier and anti-hapten antibodies on the primary anti-hapten antibody response to hapten—carrier conjugates in mice. Bacterial α-amylase (BαA), Taka-amylase A (TAA) and keyhole limpet haemocyanin (KLH) were used as carrier molecules, and 2,4-dinitrophenyl (DNP) group was used as a haptenic determinant. Three groups of mice were injected intravenously with anti-carrier antiserum, anti-hapten antiserum and normal serum as the control, respectively, immediately after the immunization with the hapten—carrier conjugate. The primary anti-carrier antibody response was markedly suppressed by the passively administered anti-carrier antibody but not anti-hapten antibody. However, the primary anti-hapten antibody response was suppressed not only by passively administered anti-hapten antibody but also by the injection of anti-carrier antibody in an early period after the immunization. When anti-carrier antibody was given twice 0 and 7 days after immunization, the primary anti-hapten antibody response was markedly suppressed and the suppressive effect was observed even at a later period. In contrast, anti-hapten antibody given by the same schedule as above suppressed only the primary anti-hapten antibody response, but not the anti-carrier antibody response. Passively administered anti-carrier antibody did not suppress carrier-specific helper cell development, but still suppressed the development of B memory cells and antibody formation against carrier determinants. The antigen dose required for the development of B-cell memory was much higher than that necessary for the stimulation of T cells. Passively administered anti-carrier antibody clearly inhibited the cellular cooperation between carrier-committed helper cells and hapten-specific B cells and the augmented primary anti-hapten antibody response induced by carrier-primed T cells was clearly abolished. Furthermore, mice preimmunized with carrier showed significantly lower anti-hapten antibody response following the hapten—carrier challenge. Moreover, development of hapten-specific memory cells was also suppressed. Thus, even in the non-specific antibody-induced suppression by anti-carrier antibody, negative feedback effect of a B-cell product with anti-carrier specificity exclusively regulates the B-cell line development and differentiation.