Clonal expansion is a characteristic feature of the B-cell repertoire of patients with rheumatoid arthritis

The present study was designed to analyze the level of B-cell clonal divers ity in patients with rheumatoid arthritis by using HCDR3 (third complementa rity determining region of the rearranged heavy chain variable region gene) length as a marker. A modified immunoglobulin V-H gene fingerprinting meth od using either genomic DNA or complementary (c) DNA derived from B cells o f the peripheral blood, synovial fluid, and tissues of several rheumatoid a rthritis patients was employed. These assays permitted the detection and di stinction of numerically expanded B-cell clones from activated but not nume rically expanded B-cell clones. The present data suggest that B-cell clonal expansion is a common and characteristic feature of rheumatoid arthritis a nd that it occurs with increasing frequency from the blood to the synovial compartments, resulting in a narrowing of the clonal repertoire at the syno vial level. These clonal expansions can involve resting, apparently memory B cells, as well as activated B cells. Furthermore, some of these individua l expansions can persist over extended periods of time. These findings supp ort the hypothesis that a chronic ongoing (auto) immune reaction is operati ve in rheumatoid arthritis and that this reaction, at least at the B-cell l evel, may be unique to each individual joint. A determination of the target s of these autoimmune reactions may provide valuable clues to help understa nd the immunopathogenesis of this disease.