Relationship of VH and VL Genes Encoding Three Idiotypic Families of Anti-p-azobenzenearsonate Antibodies

We describe here an intrastrain, cross-reactive idiotype (CRI), CRID, associated with anti-p-azobenzenearsonate antibodies of the A/J strain of mouse and distinguishable, by some but not by all of its idiotopes, from the major anti-p-azobenzenearsonate idiotype (CRIA). Molecules carrying the CRID idiotype have heavy chain variable-segment sequences that are identical or nearly identical to that of the germ-line-encoded heavy chain variable sequence of CRIA. Their light chain variable sequences are very similar to those present in a third idiotypic family, CRIC, that is a minor CRI in the A/J strain but a major CRI in BALB/c. This appears to represent a form of combinational diversity, in which the heavy and light chain variable region genes of two unrelated idiotypic families interact to form a third family, all involving antibodies of the same antigen-binding (anti-p-azobenzenearsonate) specificity. The D region of CRID, in the six monoclonal representatives studied (three IgMs, three IgGs), is unusual in that it comprises a single amino acid--arginine or serine; there are eight amino acids in the D region of CRI+A antibodies. Three different heavy chain joining regions, JH1, JH2, and JH3, are utilized. A serological reagent was developed that identifies CRID; it was used to show that the idiotype is present in relatively high concentration, comparable to that of CRIA, in anti-p-azobenzenearsonate antibodies taken soon after primary immunization. In serum taken later CRIA greatly predominates, but CRID persists at low levels.