Xid and normal mice express a light chain-associated cross-reactive idiotype in response to (T,G)-A--L and (T,G)-A--L-mBSA.

Rabbit anti-idiotypic (Id) antibodies were prepared against purified ascites anti-(T,G)-A--L antibodies (TGB5) that had been absorbed to remove A--L-specific antibodies and were specific for (T,G)-side chain determinants. Purified rabbit anti-TGB5 Id antibodies detected an allotype-independent, light chain-associated cross-reactive Id expressed by the majority of individual mice immunized with (T,G)-A--L, (T,G)-A--L coupled to methylated bovine serum albumin (mBSA), or the linear terpolymer GAT. Primary and secondary monoclonal hybridoma protein (HP) antibodies from X/Xxid heterozygous (wild-type) mice immunized with (T,G)-A--L and/or (T,G)-A--L-mBSA were analyzed for isotypy and were grouped into eight antibody fine specificity sets defined by the patterns of direct binding to the antigens (T,G)-A--L, (Phe,G)-A--L, (T,G)-Pro--L, GT, and A--L. Analysis of these primary and secondary HP for TGB5 idiotypy showed a preferential expression of the TGB5 Id among GT+-binding HP (antibody fine specificity sets 1 through 3). All of the primary GT+-binding HP and the majority of secondary GT+-binding HP (sets 1 through 3) were TGB5 Id+. Most but not all of the TGB5 Id+ HP bound GAT. Of the side-chain-specific HP (sets 1 through 7), 78% of primary HP vs 49% of secondary HP bound GT. By these criteria, the primary HP response appears more restricted than the secondary HP response, consistent with the idea that Id diversification and antibody heterogeneity are regulated and selected events occurring during memory B cell generation. Although xid mice produce less antibody than wild-type mice to (T,G)-A--L, the TGB5 Id was produced early in the primary response by both xid and wild-type mice immunized with (T,G)-A--L or (T,G)-A--L-mBSA, and was maintained as a detectable Id in equivalent amounts in their secondary serum antibody responses. These results support the idea that distinct B cell subsets, including the xid B cell subset, share the same immunoglobulin gene repertoire.