Evidence for the presence of idiotype-bearing regulatory T cells in which idiotype expression does not show linkage to either IgH alleles or the MHC.

An anti-idiotypic antiserum was raised in rabbits to a monoclonal antibody with specificity for one of the two antigenic determinants on the ferredoxin (Fd) molecule. The monoclonal antibody (Fd-B2) was derived from fusion of spleen cells from Fd-immune B10.BR (H-2k, Ighb). Examination of an extensive number of samples of Fd-immune serum from B10.BR and other mouse strains established that the Fd-B2 idiotype is essentially never present in such sera in detectable concentrations (greater than 30 ng/ml). Administration of the anti-idiotypic antibody (anti-Fd-B2) i.v. to B10.BR mice, or treatment of B10.BR T cell-enriched populations with anti-Fd-B2 + C prior to adoptive transfer to irradiated B10.BR recipients followed by challenge with Fd resulted in a significant increase in the production of anti-Fd antibodies. This effect was specific and was not reflected by a change in expression of the Fd-B2 idiotype in the antibody produced. Similarly, injection of 10 micrograms of Fd-B2 into B10.BR mice resulted in an enhanced anti-Fd response. When similar experiments were carried out using B10.D2 mice (H-2d, Ighb), which are genetic non-responders to Fd, it was observed that treatment which anti-Fd-B2 followed by challenge with Fd resulted in production in treated animals of significant levels of antibody to Fd. Again, the antisera thus produced did not contain detectable levels of the Fd-B2 idiotype. Further experiments using high responder (H-2k) mice with Igh allotypes differing from the B10 strains (C57/BR, Igha, and RF/J, Ighc), showed that treatment of these animals with anti-Fd-B2 also resulted in a highly significant enhancement of the anti-Fd response. These data imply that the anti-idiotypic antiserum (anti-Fd-2B) is exerting its influence by acting on an id + population of T cells and that the expression of this id is not dependent on genetic linkage to either the H-2 or the Igh loci.