ASSESSMENT OF A FUNCTIONAL-ROLE OF AUTO-ANTI-IDIOTYPES IN IDIOTYPE DOMINANCE

We have used a well-defined idiotypic system, the cross-reactive idiot ype of A strain (CRI(A)) (Ab1) idiotype generated in A/J mice injected with arsonate coupled to keyhole limpet hemocyanin (ARS-KLH), to dete rmine the frequency of precursors for auto-anti-idiotypic antibodies ( auto-Ab2) in naive and immunized A/J mice by limiting dilution analysi s after polyclonal activation by lipopolysaccharide. In naive animals, the precursor frequencies of auto-Ab2 B cells were below the limit of sensitivity of the technique in the majority of A/J mice, and could b e detected in only 20 % of the animals. Upon immunization with ARS-KLH , a large increase in auto-Ab2 precursor frequency was observed. This shift in frequency was not found when A/J mice were injected with KLH alone, or when BALB/c mice, which do not express the CRI(A) idiotype, were injected with ARS-KLH. To study the functional role of the auto-A b2 B cells, we injected neonatal A/J mice with polyclonal rabbit Ab3 a ntibodies directed against a recurrent idiotype of auto-Ab2. Thereafte r, these mice were injected with ARS-KLH. Although the anti-arsonate r esponse level was normal, the CRI(A) Ab1 expression was reduced tenfol d. Thus, the suppression of auto-Ab2 affects Ab1 dominance. We further show that the presence of maternal Ab1 can strongly modify the immune response of the offspring by inducing higher levels of the idiotype a fter immunization. Furthermore, IgM anti-arsonate antibodies were dete cted before immunization with antigen. From these data, we conclude th at the affinity of antigen alone cannot explain the dominance of CRI(A ). Network selection is important in the shaping of the available repe rtoire.