Role of idiotype-anti-idiotype interactions in the induction of collagen-induced arthritis in rats

The mechanism of autoantibodies (rheumatoid factor (RF) and anti-collagen autoantibodies) induction in collagen-induced arthritis (CIA) is unknown. The study assessed the hypothesis that activation of autoantibody-producing clones is mediated by idiotype-anti-idiotype (IAI) interactions with lymphocytes on heterologous collagen. It was demonstrated that RF-containing serum of rats immunized with bovine collagen (BCII) in ELISA competes with BCII for binding to anti-BCII antibodies. Immunization of rats with Fc fragments of IgG caused not only an increase in RF levels, but also induction of antibodies to BCII and anti-collagen autoantibodies. Taken together, these facts suggest that activation of RF-producing lymphocytes in CIA model occurs through IAI interactions with anti-BCII lymphocytes. Three populations of antibodies were detected in the blood of arthritic rats: a population of antibodies reacting only with BCII, a population of antibodies reacting only with rat collagen (RCII) and a population of antibodies that can bind to both bovine and rat collagen. It was shown that RF in relation to anti-collagen autoantibodies act as anti-idiotype antibodies, and a comparative analysis of antibody production in arthritic and resistant rats demonstrated that the level of anti-collagen autoantibody production depends on the level of RF production. This suggests that RF and RF-producing lymphocytes are involved in regulation of anti-collagen autoreactive lymphocyte activity through an IAI interaction mechanism. A direct activation of autoreactive anti-RCII lymphocytes by BCII cannot be excluded, but it can be supposed that induction of anti-collagen autoreactive lymphocytes needs a signal generated in IAI interactions by RF-producing lymphocytes. This hypothesis is based on the data obtained, and not only explains the mechanism of autoreactive lymphocytes activation in the rat CIA model, but also indicates that the key regulatory element in the development of arthritis in animals is RF-producing lymphocytes. The results allow a new insight on the role of RF in the pathogenesis of rheumatoid arthritis and on seeking more effective therapeutic means. (C) 2009 Elsevier GmbH. All rights reserved.