Regulatory B10 cells are decreased in patients with rheumatoid arthritis and are inversely correlated with disease activity

OBJECTIVE: Regulatory interleukin-10 (IL-10)-producing B cells (B10 cells) have been shown to prevent and cure collagen-induced arthritis in mice. In humans, very little is known about B10 cells in rheumatoid arthritis (RA). Several B cell subsets, such as CD24(high) CD38(high) , CD24(high) CD27+, and CD5+ B cells, were suggested to be precursors of B10 cells. We aimed to analyze these B cell subsets and B10 cells in RA patients and healthy controls. METHODS: B10 cells were generated from peripheral blood mononuclear cells stimulated for 24 hours with CpG and for 4 hours with phorbol 12-myristate 13-acetate/ionomycin/brefeldin A. Intracellular B cell IL-10 was assessed by flow cytometry. Thirty-one controls and 99 RA patients were included. RESULTS: After multiple adjustments, levels of CD24(high) CD38(high) , CD24(high) CD27+, and CD5+ B cells were found to be similar in RA patients and controls. Levels of B10 cells were lower in RA patients than in controls, especially in patients with RA of \textless/=5 years' duration. Levels of B10 cells correlated inversely with the Disease Activity Score in 28 joints. This was more pronounced in patients with RA of \textless/=5 years' duration, in whom B10 cells also correlated inversely with C-reactive protein levels. Moreover, B10 cells correlated inversely with rheumatoid factor levels. CD24(high) CD38(high) and CD24(high) CD27+ B cells induced more Treg cells than did CD24(low) B cells in controls but not in RA patients. CONCLUSION: The ability of B cells to produce IL-10 was altered in RA, and this impairment influenced disease activity, biologic inflammation, and autoantibody levels, especially in patients with RA of \textless/=5 years' duration. This strongly suggests a role of B10 cells in RA initiation