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Myeloid‐derived suppressor cells (MDSCs) are key regulators of immunity that initially have been defined by their ability to potently suppress T‐cell responses. Recent studies collectively demonstrate that the suppressive activity of MDSCs is not limited to T cells, but rather affects a broad range of immune cell subsets. However, relatively few studies have assessed the impact of MDSCs on B cells, particularly in the human context. Here, we report that human monocytic MDSCs (M‐MDSCs) significantly interfere with human B‐cell proliferation and function in vitro. We further show that the inhibition occurs independent of direct cell‐contact and involves the expression of suppressive mediators such as indoleamine 2, 3‐dioxygenase (IDO), arginase‐1 (Arg1), and nitric oxide (NO). In addition, our studies demonstrate that the suppression of B cells by M‐MDSCs is paralleled by a skewing in B‐cell phenotype and gene expression signatures. M‐MDSCs induced the downregulation of key surface markers on activated B cells, including IgM, HLA‐DR, CD80, CD86, TACI, and CD95. Concurrently, M‐MDSCs but not conventional monocytes elicited alterations in the transcription of genes involved in apoptosis induction, class‐switch regulation, and B‐cell differentiation and function. In summary, this study expands our understanding of the regulatory role of M‐MDSCs for human B‐cell responses.

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