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

• Published in: Journal of autoimmunity 2016-09, Vol.73, p.64-72
• Main Authors: Hua, Charlotte, Audo, Rachel, Yeremenko, Nataliya, Baeten, Dominique, Hahne, Michael, Combe, Bernard, Morel, Jacques, Daïen, Claire
• Format: Article
• Language: English
• Subjects: Adult; Aged; Allergy and Immunology; Antibodies, Monoclonal, Humanized - therapeutic use; APRIL; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Autoimmunity - immunology; B-Cell Activating Factor - antagonists & inhibitors; B-Cell Activating Factor - metabolism; B-Cell Activation Factor Receptor - metabolism; B-lymphocytes; B-Lymphocytes, Regulatory - drug effects; B-Lymphocytes, Regulatory - immunology; B-Lymphocytes, Regulatory - metabolism; Cells, Cultured; Female; Humans; Immunology; Interferon-gamma - metabolism; Interleukin-10; Interleukin-10 - immunology; Interleukin-10 - metabolism; Leukocytes, Mononuclear; Life Sciences; Lymphocyte Activation - drug effects; Male; Middle Aged; Oligodeoxyribonucleotides - pharmacology; Recombinant Fusion Proteins - therapeutic use; Rheumatoid arthritis; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; T-Lymphocytes - immunology; Tumor Necrosis Factor Ligand Superfamily Member 13 - antagonists & inhibitors; Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2016.06.002

Abstract 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-α and IFN-γ 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.