Relationship of V/sub H/ and V/sub L/ genes encoding three idiotypic families of anti-p-azobenzenearsonate antibodies

The authors describe here an intrastrain, cross-reactive idiotype (CRI), CRI/sub D/, 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 (CRI/sub A/). Molecules carrying the CRI/sub D/ 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 CRI/sub A/. Their light chain variable sequences are very similar to those present in a third idiotypic family, CRI/sub C/, 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 CRI/sub D/, in the six monoclonal representatives studied (three IgMs, three IgGs), is unusual in that is comprises a single amino acid-arginine or serine; there are eight amino acids in the D region of CRI/sub A/+ antibodies. Three different heavy chain joining regions, J/sub H/1, J/sub H/2, and J/sub H/3, are utilized. A serological reagent was developed that identifies CRI/sub D/; it was used to show that the idiotype is present in relatively high concentration, comparable to that of CRI/sub A/, in anti-p-azobenzenearsonate antibodies taken soon after primary immunization. Quantification of CRI/sub D/ was carried out with radioimmunoassay. In serum taken later CRI/sub A/ greatly predominates, but CRI/sub D/ persists at low levels