Myeloid-derived suppressor cells modulate B-cell responses

Lelis, Felipe; Jaufmann, Jennifer; Singh, Anurag; Fromm, Katja; Teschner, Annkathrin C.; Pöschel, Simone; Schäfer, Iris; Beer‐Hammer, Sandra; Rieber, Nikolaus; Hartl, Dominik

doi:10.1016/j.imlet.2017.07.003

Cited by 62 publications

(55 citation statements)

References 36 publications

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“…In the course of immune suppression, MDSCs mediate signals via direct cell‐contact or by secretion of inhibitory molecules. We recently found that efficient suppression of B cells by PMN‐MDSCs required direct cell‐contact . To determine whether M‐MDSC‐mediated inhibition of B cells was also dependent on cell‐contact, we performed transwell‐system assays.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, our group demonstrated for the first time that PMN‐MDSCs isolated from human peripheral blood significantly interfere with B‐cell proliferation, viability, and antibody production. We found that in vitro modulation of B‐cell responses by PMN‐MDSCs mainly involves Arg1 activity and production of NO and ROS . According to our knowledge, there exist no studies dealing with the interaction of human M‐MDSCs and B cells so far.…”

Section: Introductionmentioning

confidence: 97%

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

et al. 2019

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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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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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

et al. 2019

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“…During the time of the writing of this paper, Lelis et al (13) published a report on the effects of human MDSCs on B cells, albeit about granulocyte-like MDSCs, not M-MDSCs, and in the context of healthy donors, not retrovirus-induced immunodeficiency. The authors observed that human G-MDSCs suppressed in vitro B cell proliferation in a manner that involved the mediators arginase-1, NO, and reactive oxygen species (13).…”

Section: Discussionmentioning

confidence: 99%

“…Our laboratory discovered that these M-MDSCs also strongly inhibited B cell proliferation (7) and B regulatory cell IL-10 responses (11); to our knowledge, this is the first report of MDSC-mediated suppression of B cells. Subsequently, additional evidence for B cells as targets of MDSCs has been presented (12)(13)(14), particularly in autoimmunity (15)(16)(17)(18) and during B cell lymphopoiesis (19)(20)(21). There is increasing appreciation of the role MDSCs play in viral systems (22).…”

Section: Introductionmentioning

confidence: 99%

LP-BM5 Retrovirus–Expanded Monocytic Myeloid-Derived Suppressor Cells Alter B Cell Phenotype and Function

Rastad

Green

2018

ImmunoHorizons

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“…During T-cell proliferation, enhanced aerobic glycolysis produced large amounts of lactate. Lactate enhances arginase-1 expression on myeloid-derived suppressor cells (31), which then can suppress antibody production (32,33). By decreasing lactate production, DCA may decrease arginase-1 expression and consequently enhance antibody production.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effect of the aerobic glycolysis inhibitor dichloroacetate and of the Krebs cycle inhibitor LW6 on cellular and humoral alloimmunity

et al. 2017

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Abstract. Cell metabolism is altered during T-cell and B-cell activation and differentiation. Clarifying the exact metabolic shifts may lead to the development of new immunosuppressive medications. In this study, the effect of the aerobic glycolysis inhibitor dichloroacetate (DCA) and of the Krebs cycle enzyme malate dehydrogenase 2 (MDH2) inhibitor LW6 on T-cell alloimmune clonal expansion and on alloantibody production, was evaluated. T-cell clonal expansion was assessed in two-way mixed lymphocyte reaction (MLR). Humoral alloimmunity was evaluated by the alloantibody production in one-way MLR. For this purpose, an antibody-mediated complement-dependent cytotoxicity assay was developed in which the supernatants from one-way MLRs were used against resting peripheral blood mononuclear cells (PBMCs) derived from the same individual that contributed the stimulator cells for the respective MLR. DCA had a minimum effect on alloimmune T-cell clonal expansion, whereas it increased humoral immunity significantly. LW6 decreased both alloimmune T-cell proliferation and alloantibody production. The results indicate that MDH2 may be a perfect target for the development of new immunosuppressive medications, especially when inhibition of both cellular and humoral alloimmunity is desirable.

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Myeloid-derived suppressor cells modulate B-cell responses

Cited by 62 publications

References 36 publications

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

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

LP-BM5 Retrovirus–Expanded Monocytic Myeloid-Derived Suppressor Cells Alter B Cell Phenotype and Function

Comparison of the effect of the aerobic glycolysis inhibitor dichloroacetate and of the Krebs cycle inhibitor LW6 on cellular and humoral alloimmunity

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