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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-017-0798-5) contains supplementary material, which is available to authorized users.