Clonal expansion is a characteristic feature of the B-cell repetoire of patients with rheumatoid arthritis.
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
Itoh
K
K
Department of Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, New York 11030, USA.
Patki
V
V
Furie
R A
RA
Chartash
E K
EK
Jain
R I
RI
Lane
L
L
Asnis
S E
SE
Chiorazzi
N
N
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002999:Clone Cells; D004247:DNA / Q000032:analysis; D016172:DNA Fingerprinting; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology
D007135:Immunoglobulin Variable Region; D012313:RNA; D004247:DNA