Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro

Autor: Annkathrin C. Teschner, Sandra Beer-Hammer, Katja Fromm, Nikolaus Rieber, Dominik Hartl, Felipe J.N. Lelis, Jennifer Jaufmann
Rok vydání: 2019
Předmět:
Zdroj: European Journal of Immunology. 50:33-47
ISSN: 1521-4141
0014-2980
Popis: 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.
Databáze: OpenAIRE
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