Monoclonal antibodies defining a minor and a private idiotope on human rheumatoid factors

Two mouse monoclonal antibodies (mAb A216-5 and L 49-3) with antiidiotypic activity against two human monoclonal IgM rheumatoid factors (IgM RFs) were defined. Each of these monoclonal antibodies (two mouse IgG 1 K) reacted with an idiotope located on the heavy chain of the immunizing monoclonal IgM RF and was able to inhibit RF fixation to the antigen. These monoclonal antibodies did not react with other monoclonal IgM RFs from patients with macroglobulinemias or cryoglobulinemias and, therefore, did not recognize the known cross-reactive idiotopes of human monoclonal RFs. The presence of both 216-5 and 49-3 idiotopes on polyclonal IgM RFs from unrelated patients was undetectable by the inhibition assays. However, using a four-stage solid-phase radioimmunoassay, the 216-5 idiotope (minor), but not the 49-3 idiotope (private), was frequently present at a low concentration on polyclonal IgM RFs from patients suffering from rheumatoid arthritis, primary Sjögren syndromes, various infectious diseases, systemic vasculitis, and sarcoidosis and during aging. Interestingly, the 216-5 idiotope was undetectable among polyclonal IgM RFs of 12 normal adults. The main conclusions of these data are the following. (1) The definition of minor and private idiotopes of human RFs requires the use of assays able to detect low amounts of antibodies among polyclonal Ig. (2) The anti-IgG B cells which are sometimes clonally expanded during Waldenström diseases and cryoglobulinemias can also be activated during nonneoplastic diseases, among the other RF-secreting B cells. (3) Thein vivo expression of the IgM RF repertoire is different among normal adults and during various known IgM RF-inducing conditions.