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OP0114 A Proliferative Inducing Ligand (April) Promotes IL-10 Production by Human B Cells
  1. C. Hua1,
  2. R. Audo2,
  3. M. Hahne2,
  4. B. Combe1,
  5. J. Morel1,
  6. C. Daïen1
  1. 1Rheumatology department, Lapeyronie hospital
  2. 2UMR 5535, IGMM, Montpellier, France

Abstract

Background 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 a proliferation inducing ligand (APRIL) transgenic mice are protected against collagen induced arthritis.

Objectives We aimed to explore the effect of APRIL on normal human B cell IL-10 production.

Methods CpG induced IL-10 B cell production was compared in presence or absence of APRIL and B lymphocyte stimulating factor (BLys). The expression of the BLyS and APRIL receptor transmembrane activator and CAML interactor (TACI) and of BLyS specific receptor (BAFF-R) was compared between IL-10 producing and non-producing B cells. The effect of APRIL stimulated B cells on T cell cytokine production was analyzed after 3 days of co-culture. Signaling pathways of B cells activated by CpG and APRIL were analyzed by western blot. Similar experiments were performed on cells of RA patients.

Results APRIL but not BLyS promotes IL-10 production by B cells (9.5 [6.8-13.2] vs 6.2 [3.9-7.0] vs 4.2 [3.3-8.0] % for APRIL, BLyS and culture medium alone respectively, APRIL vs media p=0.002 and APRIL vs BLyS p=0.007).The effect was abrogated by co-culturing of TACI-Fc. IL-10 producing B cells expressed significantly more TACI (7.1 [5.5-16.8] vs 2.4 [1.9-7.8]%; p=0.016) and less BAFF-R (2.3 [2.0-2.5] vs 2.7 [2.3-2.8] of mean fluorescence intensity; p=0.021) than non- IL-10 producing B cells. APRIL stimulated B cells decreased TNF-α (-36±13%, p=0.02) and IFN-γ (-14±3%; p=0.02) secretion of T cells compared to non-stimulated B cells but not IL-17 production (-14±14%, p=0.31). APRIL further stimulated CpG activated STAT3, ERK and JNK pathways. APRIL also promoted IL-10 production of B cells in RA patients and similar pattern of APRIL and BLyS receptors on IL-10 producing B cells were observed in RA patients and in controls.

Conclusions We show for the first time that APRIL but not BLyS promotes IL-10 production by B cells and enhances the regulatory role of B cells on T cells by decreasing TNF-a and IFN-g by T cells. IL-10 producing B cells of RA patients are responsive to APRIL suggesting a possible therapeutic application by expanding B10 cells of these patients.

Disclosure of Interest None declared

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