The repertoire of antibodies to a hapten group in an inbred strain of mouse.

We have investigated the diversity of antibodies to the p-azophenylarsonate (Ar) hapten group in the A strain of mouse. The method used consisted of suppressing an idiotype which commonly is observed in the anti-Ar antibodies of all this strain, and then generating anti-idiotypic antisera against the anti-Ar antibodies (lacking the cross-reactive idiotype) which arose after hyperimmunization of the suppressed mice. Anti-idiotypic antibodies prepared against these anti-Ar antibodies were used as a tool to investigate the frequency of recurrence of individual idiotypes in other mice of the same strain. A highly sensitive radioimmunoassay indicated that 3 of the 4 idiotypes studied were virtually undetectable in a panel of 181 A/J mice immunized against the phenylarsonate hapten. A fourth idiotype was found but at very low frequency. The results emphasize the enormous diversity of the immune response to a single hapten group within a strain of mouse. They are interpreted on the basis of hypothesis that the diversity arises through a random series of somatic events. The common cross-reactive idiotype, which is present in the anti-Ar antibodies of all normal A/J mice, is postulated to be the product of a germ-line gene which is closely related to a germ-line gene through a small number of somatic mutations which takes place in every A/J mouse.