anti-idiotypic antibody directly induce idiotype or facilitate an enhancement of idiotype expression during subsequent antigenic stimulation. Higher doses of anti- idiotypic antibody promote suppression of idiotype

Regulation of immune responsiveness has been attributed theoretically (1, 2) and experimentally (3, 4) to interactions between idiotypic and anti-idiotypic structures. Constituents of this idiotype network can be induced and triggered without the intervention of external antigens (5-10). For instance, anti-idiotypic antibodies can mimic specific antigen to promote the induction (9, 10) or suppression (5-7) of synthesis of the idiotypic antibody in the absence of antigen. In general, low doses of anti-idiotypic antibody directly induce idiotype or facilitate an enhancement of idiotype expression during subsequent antigenic stimulation. Higher doses of antiidiotypic antibody promote suppression of idiotype expression (3, 11). In the antigen-specific response to the p-azobenzenearsonate (ABA) 1 hapten group, a large proportion of the anti-ABA antibodies induced in A/J mice share a crossreactive idiotype (CRI) (12) representing a nonidentical, but closely related, family of idiotypic determinants (13-16). Immunoregulation of this idiotype has been demonstrated by two approaches. First, anti-idiotypic antibodies have been passively administered, resulting in the suppression of the level of CRI + antibodies (6, 17, 18) and the induction of idiotype-specific suppressor T cells (T~) (17-19). Second, CRI ÷ serum antibodies (20, 21) or CRI + hybridoma proteins (HP) (22) covalently coupled to syngeneic lymphocytes have been used to induce idiotype-specific Ts and depress both the production of CRI + antibodies (20, 22) and delayed-type hypersensitivity to antigenic challenge (21). With both approaches, the production of total circulating anti-ABA antibodies is not substantially altered (6, 17, 18, 20, 22). Most attempts to investigate the regulation of idiotype expression have involved the creation of an artificial network by the passive administration of anti-idiotypic antibody or of the idiotype in adjuvant. However, in a few cases idiotypic modulation has been demonstrated during the development of an antibody response to specific antigen (8, 11, 23, 24). In this paper, an attempt was made to investigate the regulation of idiotype by an