Enhancement and suppression of an intrastrain cross-reactive idiotype

The effects of a copolymer of monoclonal anti-idiotype (7B7.10) with keyhole limpet haemocyanin (KLH), designated 7-K, on an ongoing immune response were investigated. It was found that the response could be diverted to the production of higher titres of anti-p-azobenzenearsonate (Ar) antibodies, of which nearly 100% carry an intrastrain cross-reactive idiotype (CRIA). The effect was observed only in mice that had received a pre-inoculation of KLH-Ar, or KLH plus bovine gamma globulin-Ar (BGG-Ar). The effect was also observed, however, when cross-linked 7B7.10 was mixed, rather than conjugated with KLH, suggesting that the role of KLH was to induce the production of a B-cell growth factor. Cross-linked 7B7.10 was not effective in the absence of KLH. A primary inoculation of 7-K together with KLH-Ar did not result in significant suppression or enhancement of CRIA. Also, pre-inoculation of 7-K alone did not suppress a subsequent idiotypic response to KLH-Ar, whereas monomeric anti-Id was suppressive. This supports a possible role for the unmodified Fc segment in the suppressive mechanism. In mice primed with KLH-Ar, before administration of 7-K, CRI+A molecules lacking anti-Ar activity were present in very low concentrations in the immune sera. Larger quantities of such molecules were present in the sera of mice that received 7-K alone. The methods described permit the reproducible production of large amounts of CRI+A anti-Ar antibodies.