Heterogeneity of an intrastrain cross-reactive idiotype associated with anti-p-azophenylarsonate antibodies of A/J mice.

Hybridomas were prepared with spleen cells of A/J mice immunized with KLH-Ar and a nonsecreting tumor cell line. Of the hybridomas secreting anti-Ar antibodies, approximately 25% expressed the major cross-reactive idiotype (CRI). All subclasses of IgG and an IgM protein were represented among the CRI-positive hybridoma products (HP) generated with cells of a single mouse. Serologic analysis showed that purified CRI-positive HP are heterogeneous with respect to the expression of idiotypic determinants. Fourteen CRI-positive HP could be divided into at least four groups on the basis of their widely varying inhibitory capacities in the conventional radioimmune assay for the CRI. Further evidence for heterogeneity was obtained with anti-idiotypic reagents prepared against four CRI-positive HP. Two HP were found to possess unique or “private” determinants that are not present on any of the other HP examined or in a pool of other HP. One also possesses idiotypic determinant(s) not found in a pool of A/J anti-Ar antibodies. The finding that some individual HP can almost completely displace A/J serum anti-Ar antibody from its anti-idiotype indicates that conventional anti-idiotypic antibodies are elicited mainly in response to the shared, or “public” idiotypic determinants in pooled serum anti-Ar antibodies. It further shows that CRI-positive serum antibody molecules possess at least one idiotypic determinant in common with such HP and, therefore, with one another. The data indicate that serum antibodies identified as CRI-positive are idiotypically heterogeneous but share cross-reactive determinants.