Cooperation between antigen-reactive T cells and anti-idiotypic B cells in the anti-idiotypic response to antigen-antibody complexes

Abstract

THE variable regions of antibody molecules carry unique antigenic determinants (idiotypes), which have been shown to be isoimmunogenic, that is, immunogenic in syngeneic animals1–3. Jerne and others4,5 have proposed that autoimmune responses to self-idiotypes might form the basis of an immunoregulatory network, and evidence in favour of this hypothesis has been reported from several laboratories6–8. Preformed antigen–antibody complexes of dinitrophenylated keyhole limpet haemocyanin (DNP-KLH) and the DNP-binding myeloma protein M315 are very effective in inducing iso-anti-idiotypic antibodies to the M315 idiotype in BALB/c mice9, and formation of immune complexes during an antibody response could therefore represent the mechanism whereby self-idiotypes become autoimmunogenic. As such anti-idiotypic antibody responses are T-cell-dependent, one must assume that if animals are immunised with purified antibody then anti-idiotypic T (helper) cells cooperate with anti-idiotypic B cells. The existence of iso-anti-idiotypic T cells has been formally demonstrated10,11. When an antibody is administered as an immune complex, a similar cooperative event may occur; but it is also possible that antigen-specific T cells cooperate with idiotype-specific B cells through the immune complex, as the latter can prime animals for immunity to the antigen12 and to idiotypic determinants on the antibody (see below). Here I present evidence that this occurs.