IL-10 induces TGF-β secretion, TGF-β receptor II upregulation, and IgA secretion in B cells

Background: Interleukin-10 (IL-10) is a pleiotropic cytokine, which has both regulatory and stimulatory effects on different immune cell types. Different studies have reported the importance of IL-10 and Transforming growth factor-beta (TGF-p) in the regulation of B cell class switching the production of immunoglobulin A (IgA); however, the underlying mechanisms remain to be fully elucidated. The objective of this study was to investigate the TGF-p response during B stimulation of human B cells by IL-10. Methods: Pan B cells of healthy donors were negatively purified by a magnetic cell separation technique. B cells were cultured with multimeric CD40 ligand (mCD40L) and IL-10 for two and seven days. After harvesting in specific days, TGF-p receptor II and surface IgA expression was determined by flow cytometry, while IgA and TGF-p secretion was assessed by enzyme-linked immunosorbent assay. Results: B cells endogenously expressed TGF-p receptor II and after 48 hours cultivation with mCD40L or mCD40L plus IL-10, both the expression of this receptor and the production of TGF-p were significantly increased. Notably, TGF-p levels following stimulation with mCD40L and IL-10 were higher than those produced by B cells stimulated with mCD40L alone. Furthermore, at day 7 and following IL-10 stimulation, there was a significant rise in the amount of IgA secretion by class-switched plasma cells, which was higher than stimulation with mCD40L alone. Conclusion: Our findings suggest that IL-10 can modulate TGF-p production and TGF-p receptor expression in mCD40-activated human B lymphocytes.