Abstract
BACKGROUND: Involvement of B cells in the pathogenesis of rheumatoid arthritis (RA) is supported by the presence of disease-specific autoantibodies and the efficacy of treatment directed against B cells. B cells that express low levels of or lack the B cell receptor (BCR) co-receptor CD21, CD21(-/low) B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21(+) and CD21(-/low) B cell subsets in newly diagnosed, early RA (eRA) patients and investigated whether any of the B cell subsets were associated with autoantibody status, disease activity and/or joint destruction. METHODS: Seventy-six eRA patients and 28 age- and sex-matched healthy donors were recruited. Multiple clinical parameters were assessed, including disease activity and radiographic joint destruction. B cell subsets were analysed in peripheral blood (PB) and synovial fluid (SF) using flow cytometry. RESULTS: Compared to healthy donors, the eRA patients displayed an elevated frequency of naïve CD21(+) B cells in PB. Amongst memory B cells, eRA patients had lower frequencies of the CD21(+)CD27(+) subsets and CD21(-/low) CD27(+)IgD(+) subset. The only B cell subset found to associate with clinical factors was the CD21(-/low) double-negative (DN, CD27(-)IgD(-)) cell population, linked with the joint space narrowing score, i.e. cartilage destruction. Moreover, in SF from patients with established RA, the CD21(-/low) DN B cells were expanded and these cells expressed receptor activator of the nuclear factor κB ligand (RANKL). CONCLUSIONS: Cartilage destruction in eRA patients was associated with an expanded proportion of CD21(-/low) DN B cells in PB. The subset was also expanded in SF from established RA patients and expressed RANKL. Taken together, our results suggest a role for CD21(-/low) DN in RA pathogenesis.