Transcriptomics Identify CD9 as a Marker of Murine IL-10-Competent Regulatory B Cells

•RNA profiling identifies key factors correlated with Breg biogenesis and function•IL-10competent B cells and their progenitors are distinguished by CD9•CD9 promotes suppressive function of IL-10competent Breg cells

SummaryRegulatory B cells (Breg) have immune suppressive functions in various autoimmune/inflammation models and diseases and are found to be enriched in diverse B cell subsets. The lack of a unique marker or set of markers efficiently identifying Breg cells impedes detailed investigation into their origin, development, and immunological roles. Here, we perform transcriptome analysis of IL-10-expressing B cells to identify key regulators for Breg biogenesis and function and identify CD9, a tetraspanin-family transmembrane protein, as a key surface marker for most mouse IL-10+ B cells and their progenitors. CD9 plays a role in the suppressive function of IL-10+ B cells in ex vivo T cell proliferation assays through a mechanism that is dependent upon B/T cell interactions. CD9+ B cells also demonstrate inhibition of Th1-mediated contact hypersensitivity in an in vivo model system. Taken together, our findings implicate CD9 in the immunosuppressive activity of regulatory B cells.

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