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J Autoimmun. 2016 Sep;73:64-72. doi: 10.1016/j.jaut.2016.06.002. Epub 2016 Jun 29.

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

Author information

1
Department of Rheumatology, Lapeyronie Hospital and Montpellier University, Montpellier, France; UMR5535, IGMM, CNRS, Montpellier, France.
2
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
3
UMR5535, IGMM, CNRS, Montpellier, France; Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
4
Department of Rheumatology, Lapeyronie Hospital and Montpellier University, Montpellier, France; UMR5535, IGMM, CNRS, Montpellier, France. Electronic address: c-daien@chu-montpellier.fr.

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.

KEYWORDS:

APRIL; B-lymphocytes; Interleukin-10; Rheumatoid arthritis

PMID:
27372914
DOI:
10.1016/j.jaut.2016.06.002
[Indexed for MEDLINE]

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