Idiotypic regulation of the immune system by the induction of antibodies against anti-idiotypic antibodies.

Anticarbohydrate antibodies (Ab1) were isolated from a rabbit hyperimmunized with Micrococcus lysodeikticus and injected into allotype-matched rabbits in order to obtain specific anti-iodiotypic antibodies (Ab2). Ab2 was isolated by means of a Sepharose column coupled to the anticarbohydrate antibodies and was injected into two allotype-matched rabbits. These latter rabbits produced specific anti-anti-idiotypic antibodies (Ab3) probably sharing idiotypic specificities with Ab1. However, these Ab3 did not react with the antigenic carbohydrate moiety of bacteria. The two rabbits that had produced Ab3 were then immunized with M. lysodeikticus and synthesized anticarbohydrate antibodies (Ab1') bearing idiotypic specificities similar to those of Ab1. The immune repertoire which is effectively expressed in one individual depends not only on the antigenic stimulation but also on the previous idiotypic history of the individual. These data support the concept that the immune system is a functional idiotypic network.