Cartilage destruction in early rheumatoid arthritis patients correlates with CD21^-/low double-negative B cells

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.

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.

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).

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.