Antiidiotypic activity in the IgM fractions of mixed cryoglobulins.

To search for human antiidiotypic antibodies, cryoglobulins from 11 patients with mixed cryoglobulinemia, 7 of whom had evidence of prior hepatitis B virus infection were separated on Sephadex G-200. Each of the IgM, 8 of which were IgM kappa, was tested with the F(ab')2 fragments prepared from each of the IgG fractions in a solid phase assay by using binding of 125I Staph A protein after the addition of rabbit anti-IgM. Unlike rabbit anti-Fab, which reacted approximately to the same extent with all F(ab')2 fragments, the IgM varied in their binding to F(ab')2 fragments, reacting with 2 to 10 antigens. Nine reacted with their autologous antigen and in 5 instances autologous reactivity exceeded that with heterologous F(ab')2 fragments. Reactivity was not related to prior exposure to HBV. Though absorption with Cohn fraction II F(ab')2 fragments generally abolished reactivity, 1 IgM protein continued to react with nine F(ab')2 fragments and 4 others with the F(ab')2 fragment from a single patient. Even when they contained only a single type of kappa-chain, the IgM appeared to contain multiple antibodies since absorption with solid phase Fc fragments or IgG removed anti-Fc rheumatoid factor activity but failed to affect binding to F(ab')2 fragments. Five of 7 IgM were able to bind the Fv region of a monoclonal IgM kappa-protein. Some of the anti-Fab antibodies were directed against idiotypes since addition of HbsAg to F(ab')2 fragments from HBsAb-positive IgG resulted in a marked decrease in binding of the IgM fraction in 6 out of 7 studies, whereas no decrease was noted in 6 experiments with F(ab')2 fragments that were HBsAb negative. The possible existence of antibodies against other idiotypes or other determinants in the Fab region cannot be excluded.