Idiotypes of anti-Ia antibodies. II. Effects of in vivo treatment with xenogeneic anti-idiotype.

The effects of in vivo treatment with xenogeneic anti-idiotypic antibodies were examined in an anti-Ia idiotypic system. Monoclonal antibody 14-4-4S, specific for Ia.7, has been shown to bear idiotopes that are expressed at readily detectable levels in conventional alloantibody responses. Sera from mice treated with purified anti-idiotypic antibodies (anti-Id) were found to contain inhibitory activity in an ELISA specific for the 14-4-4S Id, whereas sera from control mice treated with heterologous normal Ig did not. In addition, sera of anti-Id-treated C3H.SW mice contained specific anti-I-E activity, shown by binding to B10.A(2R) but not B10.A(4R) LPS blasts in flow microfluorometry. The anti-I-E induced by anti-Id included more IgG1 than IgG2. Even though a significant amount of anti-I-E activity was present in the serum, absorption analysis showed that most of the idiotope-positive antibody was not I-Ek-specific. Penetrance of induction of anti-I-E by anti-Id was 100% in the C3H.SW mice tested, and activity persisted in the serum for at least 8 to 9 mo in some cases. B10 mice produced only marginal anti-I-E activity after treatment, suggesting that induction is due to specific triggering rather than due entirely to a resemblance of anti-Id to the I-E antigen. The results thus indicate long-lasting alterations in an anti-Ia idiotypic system in the absence of exposure to conventional antigen, and represent specific manipulation of anti-Ia immunity.