Activation of human B cells negatively regulates TGF-β1 production

Background: accumulating evidence indicate that b cells can exhibit pro- or anti-inflammatory activities. similar to interleukin (il)-10-competent b cells,we recently showed that transforming growth factor (tgf)-β1-producing regulatory b cells limit the induction of autoimmune neuroinflammation in mice,making them potentially important in maintaining peripheral immune tolerance in central nervous system inflammatory demyelinating disorders such as multiple sclerosis. methods: in this study,we compared b cell production of tgf-β1 and il-10,the two most studied regulatory cytokines,and the pro-inflammatory b cell-derived il-6 and tumor necrosis factor cytokines under basal conditions and following polyclonal stimulation with dual b cell receptor (bcr) cross-linking and toll-like receptor (tlr)9 engagement. results: we showed that resting tgf-β1-producing b cells fall within both the naïve (cd27-) and memory (cd27+) b cell compartments. we found no spontaneous b cell-derived il-10,il-6 or tumor necrosis factor (tnf) production. human b cell activation with anti-ig antibodies plus cpg-b leads to only modest il-10 production by memory cd19+cd27+ b cells while expression levels of il-6 and tnf by both naive and memory b cells were strongly induced. remarkably,stimulated b cells showed significantly reduced capacity to produce tgf-β1. conclusions: these findings indicate that b cell activation may facilitate the development of excessive immune responses and autoimmunity by restricting b cell-derived tgf-β1 production by resting b cells and favoring in turns the proinflammatory actions of activated cytokine-producing b cells. © 2017 the author(s).