Reduced CD 5 + CD 24 hi CD 38 hi and interleukin‐10 + regulatory B cells in active anti‐neutrophil cytoplasmic autoantibody‐associated vasculitis permit increased circulating autoantibodies

Summary Pathogenesis of anti‐neutrophil cytoplasmic autoantibody (ANCA) ‐associated vasculitis is B cell‐dependent, although how particular B cell subsets modulate immunopathogenesis remains unknown. Although their phenotype remains controversial, regulatory B cells ( B regs ), play a role in immunological tolerance via interleukin ( IL) ‐10. Putative CD 19 + CD 24 hi CD 38 hi and CD 19 + CD 24 hi CD 27 + B regs were evaluated in addition to their CD 5 + subsets in 69 patients with ANCA‐associated vasculitis (AAV) . B cell IL ‐10 was verified by flow cytometry following culture with CD 40 ligand and cytosine–phosphate–guanosine ( CpG) DNA . Patients with active disease had decreased levels of CD 5 + CD 24 hi CD 38 hi B cells and IL‐ 10 + B cells compared to patients in remission and healthy controls ( HC s). As IL ‐10 + and CD 5 + CD 24 hi CD 38 hi B cells normalized in remission within an individual, ANCA titres decreased. The CD 5 + subset of CD 24 hi CD 38 hi B cells decreases in active disease and rebounds during remission similarly to IL ‐10‐producing B cells. Moreover, CD 5 + B cells are enriched in the ability to produce IL ‐10 compared to CD 5 neg B cells. Together these results suggest that CD 5 may identify functional IL ‐10‐producing B regs . The malfunction of B regs during active disease due to reduced IL ‐10 expression may thus permit ANCA production.