Production of auto-anti-idiotypic antibody during the normal immune response. IV. Studies of the primary and secondary responses to thymus-dependent and -independent antigens.

We have previously shown that hapten-augmentable plaque-forming cells are cells whose secretion of antibody is inhibited by the binding of auto-anti-idiotype antibody to cell surface antigen receptors. Using hapten augmentation of plaque formation, it was shown in the present report that auto-anti-idiotype antibodies are produced during the primary and secondary responses to both thymus-dependent und thymus-independent antigens. In the secondary response to the T-independent antigen trinitrophenylated Ficoll, the rate of appearance of auto-anti-idiotype antibody was faster, and the number of hapten-augmentable plaques was greater than in the primary response suggesting an anamnestic auto-anti-idiotype response. With the T-dependent antigen, trinitrophenylated bovine gamma-globulin, the kinetics and magnitude of the auto-anti-idiotypic antibody response were relatively similar in the primary and secondary responses. However, a lower concentration of hapten was required to reveal the hapten-augmentable plaques in the secondary response. This is in keeping with the usual finding that secondary antibody to T-dependent antigens is of very high affinity. Both direct and indirect hapten-augmentable plaque-forming cells were detected suggesting that the secretion of both IgM and IgG antibodies is regulated by auto-anti-idiotype antibodies. The data are consistent with a role for auto-anti-idiotype antibody in the normal down-regulation of the immune response as suggested by Jerne's network hypothesis.