A proliferation inducing ligand (APRIL) promotes IL-10 production and regulatory functions of human B cells

B cells may have a negative regulatory role, mainly mediated by interleukin 10 (IL-10). We recently showed that regulatory B-cell functions are impaired in patients with rheumatoid arthritis (RA) and that mice transgenic for a proliferation-inducing ligand (APRIL) are protected against collagen-induced arthritis. We aimed to explore the effect of APRIL on human B-cell IL-10 production, in healthy subjects and in patients with RA. The IL-10 production of B-cell was greater with APRIL than with BLyS or control medium, in a dose dependent manner. TACI expression was greater in IL-10 producing B cells (B10) than non-IL-10-producing B cells whereas BAFF-R expression was lower. TNF-alpha and IFN-gamma secretion of T-cells were decreased by APRIL-stimulated B cells. APRIL stimulated STAT3 and STAT3 inhibition decreased B10 cells. APRIL also promoted B10 cells in RA patients. In conclusion, APRIL but not BLyS promotes IL-10 production by CpG-activated B cells and enhances the regulatory role of B cells on T cells. B10 cells in RA patients are responsive to APRIL, which suggests a possible therapeutic application of APRIL to expand B10 cells. This could also explain the difference of clinical efficacy observed between belimumab and atacicept in RA. (C) 2016 Elsevier Ltd. All rights reserved.