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 animals^1–3. Jerne and others^4,5 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 laboratories^6–8. 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 demonstrated^10,11. 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.