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

• Published in: Arthritis research Vol. 2; no. 1; pp. 50 - 58
• Main Authors: Itoh, K, Patki, V, Furie, R A, Chartash, E K, Jain, R I, Lane, L, Asnis, S E, Chiorazzi, N
• Format: Journal Article
• Language: English
• Published: England 2000
• Subjects: Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Clone Cells; DNA - analysis; DNA Fingerprinting; Humans; Immunoglobulin Variable Region - genetics; Polymerase Chain Reaction; RNA - analysis; Synovial Fluid - cytology; Synovial Fluid - immunology; Synovial Membrane - immunology; Synovial Membrane - pathology
• ISSN: 1465-9905; 1465-9913

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 VH 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