Research article

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

Kenji Itoh, Varsha Patki, Richard A Furie, Elliot K Chartash, Rita I Jain, Lewis Lane, Stanley E Asnis and Nicholas Chiorazzi

North Shore University Hospital, New York University School of Medicine, Manhasset, New York, USA

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Arthritis Res 2000, 2:50-58doi:10.1186/ar68

Published:	1 December 1999

Abstract

The present study was designed to analyze the level of B-cell clonal diversity in patients with rheumatoid arthritis by using HCDR3 (third complementarity determining region of the rearranged heavy chain variable region gene) length as a marker. A modified immunoglobulin V_H gene fingerprinting method using either genomic DNA or complementary (c)DNA derived from B cells of the peripheral blood, synovial fluid, and tissues of several rheumatoid arthritis patients was employed. These assays permitted the detection and distinction of numerically expanded B-cell clones from activated but not numerically expanded B-cell clones. The present data suggest that B-cell clonal expansion is a common and characteristic feature of rheumatoid arthritis and that it occurs with increasing frequency from the blood to the synovial compartments, resulting in a narrowing of the clonal repertoire at the synovial level. These clonal expansions can involve resting, apparently memory B cells, as well as activated B cells. Furthermore, some of these individual expansions can persist over extended periods of time. These findings support the hypothesis that a chronic ongoing (auto)immune reaction is operative in rheumatoid arthritis and that this reaction, at least at the B-cell level, may be unique to each individual joint. A determination of the targets of these autoimmune reactions may provide valuable clues to help understand the immunopathogenesis of this disease.