Reduced CD5+CD24hiCD38hi 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 (Bregs), play a role in immunological tolerance via interleukin (IL)‐10. Putative CD19+CD24hiCD38hi and CD19+CD24hiCD27+ Bregs were evaluated in addition to their CD5+ subsets in 69 patients with ANCA‐associated vasculitis (AAV). B cell IL‐10 was verified by flow cytometry following culture with CD40 ligand and cytosine–phosphate–guanosine (CpG) DNA. Patients with active disease had decreased levels of CD5+CD24hiCD38hi B cells and IL‐10+ B cells compared to patients in remission and healthy controls (HCs). As IL‐10+ and CD5+CD24hiCD38hi B cells normalized in remission within an individual, ANCA titres decreased. The CD5+ subset of CD24hiCD38hi B cells decreases in active disease and rebounds during remission similarly to IL‐10‐producing B cells. Moreover, CD5+ B cells are enriched in the ability to produce IL‐10 compared to CD5neg B cells. Together these results suggest that CD5 may identify functional IL‐10‐producing Bregs. The malfunction of Bregs during active disease due to reduced IL‐10 expression may thus permit ANCA production.