B Cell Clonal Expansion and Somatic Hypermutation of Ig Variable Heavy Chain Genes in the Synovial Membrane of Patients with Osteoarthritis

Journal of Immunology - Tập 178 Số 1 - Trang 557-565 - 2007
Reng-Rong Da1, Yingzhi Qin2, Dominique Baeten3, Yiping Zhang2
1Department of Neurology, University of California, Irvine, Irvine, CA 92697, USA
2*Department of Neurology, University of California Irvine, Irvine, CA 92697; and
3Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, The Netherlands

Tóm tắt

Abstract Inflammatory mediators have been explored as possible factors in the initiation and/or progression of osteoarthritis (OA). This study shows that synovial infiltration by B lymphocytes is present in almost half of the knee OA cases. The degree of B lymphocyte infiltration is associated with more pronounced synovial inflammation and with the presence of plasma cells and lymphoid follicles in more severe cases. To examine whether these B cells are merely bystanders or could be involved in the pathogenesis of OA, we analyzed the Ig H chain variable region (VH) genes of B cells recovered from the synovial membrane of five OA patients with marked B cell infiltration. Sequence analysis of CDR3 regions of rearranged VDJ genes revealed clonal or oligoclonal B cell expansions in all cases. Expanded B cell clones in four of five OA patients showed clustered somatic mutations, occurring mainly in the CDRs and with a high replacement-to-silent ratio (>2.9), indicating that these cells are postgerminal center B cells that had been positively selected through their Ag receptor. These data demonstrate the presence in inflamed knee OA synovium of clonally expanded, Ag-driven B cells that may contribute to the development or progression of the disease.

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Journal of Immunology

Tập 178 Số 1

557-565

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