Idiotypes and autoimmunity

By the analysis of hybridomas constructed from B cells early in development we have shown that: (i) the early neonatal B cell repertoire consists of a highly autoreactive set of B cells showing extensive multispecificity and interconnectivity; (ii) many of these antibodies express anti-idiotypic activity towards autologous germline-encoded idiotypic antibodies; (iii) the anti-idiotypic activities of such B cells and/or their antibody products play a major role in establishing the clonal dominance of certain well-characterized idiotypes in the responses to phosphorylcholine (PC) and alpha 1----3 dextran; and (iv) results obtained in comparisons between antibodies to the acetylcholine receptor and alpha 1----3 dextran in humans and mice showed extensive idiotypic connectivity. Some of the anti-idiotypic specificities involved were also apparent in the neonatally derived antibodies. These results suggest that there are extensive idiotype-directed interactions between B cells early in development which appear to be essential for establishing the adult B cell repertoire and the accompanying clonal dominance of appropriate idiotypes. Similar interactions may also play a role in the development of certain autoimmune disorders.