Retinoic acid‐producing, ex‐vivo ‐generated human tolerogenic dendritic cells induce the proliferation of immunosuppressive B lymphocytes

Summary While much is known about tolerogenic dendritic cell effects on forkhead box protein 3 ( F ox P 3) + regulatory T cells, virtually nothing is known about their effects on another arm of immunoregulation that is mediated by a subpopulation of immunosuppressive B cells. These cells suppress rheumatoid arthritis, lupus and inflammatory bowel disease in mice, and functional defects have been reported in human lupus. We show that co‐stimulation‐impaired tolerogenic dendritic cells that prevent and reverse type 1 diabetes mellitus induce the proliferation of human immunosuppressive B cells in vitro . We also show that the suppressive properties of these B cells concentrate inside the CD 19 + CD 24 + B cell population and more specifically inside the CD 19 + CD 24 + CD 38 + regulatory B cell population. We discovered that B cell conversion into suppressive cells in vitro is partially dependent on dendritic cell production of retinoic acid and also that CD 19 + CD 24 + CD 38 + B regulatory cells express retinoic acid receptors. Taken together, our data suggest a model whereby part of the immunosuppressive properties of human tolerogenic dendritic cells could be mediated by retinoic acid which, in addition to its known role in favouring T cell differentiation to F ox P 3 + regulatory T cells, acts to convert B cells into immunosuppressive cells.