The Unknown Aspect of BAFF: Inducing IL-35 Production by a CD5+CD1dhiFcγRIIbhi Regulatory B-Cell Subset in Lupus

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Abstract

IL-35 is a critical immunosuppressive cytokine that plays an important role in various autoimmune diseases. The purpose of this study was to determine whether BAFF, a key pathogenic factor in systemic lupus erythematosus, also a dichotomous regulator for B-cell immune responses, has an effect on IL-35–producing regulatory B cells and their underlying mechanisms in lupus. We found that exogenous BAFF could induce IL-35 production by splenic B cells from MRL-Faslpr/lpr mice. BAFF-induced IL-35–producing B cells were mainly from the marginal zone B-cell subset and exhibited a CD5+CD1dhiFcγRIIbhi phenotype. These IL-35–producing regulatory B-cell subsets exhibited regulatory effects on both CD4+CD25– T cells and CD4+CD25+ regulatory T cells. We further identified that BAFF-TACI interaction could induce the production of IL-35 through the classical NF-κB1 pathway. In vivo study also showed that BAFF could facilitate IL-35 secretion in marginal zone B cells, whereas anti-BAFF treatment could decrease the frequency of IL-35–producing CD5+CD1dhiFcγRIIbhi B cells in MRL-Faslpr/lpr mice. We showed that BAFF could induce IL-35 production by a unique CD5+CD1dhiFcγRIIbhi regulatory B-cell subset mainly through TACI activation in lupus, providing an advanced understanding of the regulatory effect of BAFF in autoimmune diseases.

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Zhang, Y., Li, J., Zhou, N., Zhang, Y., Wu, M., Xu, J., … Tao, J. (2017). The Unknown Aspect of BAFF: Inducing IL-35 Production by a CD5+CD1dhiFcγRIIbhi Regulatory B-Cell Subset in Lupus. Journal of Investigative Dermatology, 137(12), 2532–2543. https://doi.org/10.1016/j.jid.2017.07.843

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