title: B cell clonal expansion and somatic hypermutation of Ig variable heavy chain genes in the synovial membrane of patients with osteoarthritis.
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 (V(H)) 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.
authors.affiliation: Department of Neurology, University of California Irvine, Irvine, CA 92697, USA.
authors.forename: Reng-Rong
authors.initials: RR
authors.lastname: Da
authors.forename: Yufen
authors.initials: Y
authors.lastname: Qin
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000368:Aged; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001483:Base Sequence; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D027041:Somatic Hypermutation, Immunoglobulin; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology
chemical_list: D007135:Immunoglobulin Variable Region