Induction of chronic idiotype suppression by ligands binding to the variable (not the constant) region of the idiotypic target.

It was previously shown that in C57BL/6 mice chronic suppression of an idiotypically defined subset of lambda 1 chain-bearing anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibodies is achieved by neonatal administration of allogeneic monoclonal anti-idiotope antibodies reactive with this subset, or by NP coupled to mouse immunoglobulin. The present data show that isologous monoclonal anti-idiotope antibodies have the same effect. In contrast, antibodies against constant region determinants of lambda 1, mu or delta immunoglobulin chains failed to induce chronic suppression of the same antibody subset. Furthermore, the effect of the anti-idiotope antibodies was neutralized by idiotypic antibodies of the IgG1 class, injected before or together with the anti-idiotype. These results suggest that the mere complexing of idiotypic molecules on the B cell surface or in the circulation is insufficient for the induction of chronic idiotype suppression. In the present system, induction appears to require the binding of a ligand to idiotype-bearing receptor V regions, expressed on the surface of B (or T?) cells.