IL-10-producing regulatory B cells and plasmocytes: Molecular mechanisms and disease relevance

Cerqueira, Cátia; Manfroi, Benoît; Fillatreau, Simon

doi:10.1016/j.smim.2019.101323

Cited by 48 publications

(25 citation statements)

References 94 publications

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“…We reported that BANK1 gene expression is not only decreased in GZMB + Bregs, but also in other Breg cell subtypes with different phenotypes and functions. This is concordant with the reduced level of BANK1 observed after B cell activation and in differentiated cells, as tumor B cells (GSE 22529) or plasma cells (GSE 6691), since Breg cells have also been shown to be highly differentiated cells (8,(76)(77)(78)(79)(80) and GZMB + Bregs are enriched in plasmablast population (10). Downregulation of BANK1 in these cells could be a hallmark of preplasma phenotype, common to Bregs and plasma cells.…”

Section: Discussionsupporting

confidence: 72%

Connection of BANK1, Tolerance, Regulatory B cells, and Apoptosis: Perspectives of a Reductionist Investigation

et al. 2021

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BANK1 transcript is upregulated in whole blood after kidney transplantation in tolerant patients. In comparison to patients with rejection, tolerant patients display higher level of regulatory B cells (Bregs) expressing granzyme B (GZMB+) that have the capability to prevent effector T cells proliferation. However, BANK1 was found to be decreased in these GZMB+ Bregs. In this article, we investigated seven different transcriptomic studies and mined the literature in order to make link between BANK1, tolerance and Bregs. As for GZMB+ Bregs, we found that BANK1 was decreased in other subtypes of Bregs, including IL10+ and CD24hiCD38hi transitional regulatory B cells, along with BANK1 was down-regulated in activated/differentiated B cells, as in CD40-activated B cells, in leukemia and plasma cells. Following a reductionist approach, biological concepts were extracted from BANK1 literature and allowed us to infer association between BANK1 and immune signaling pathways, as STAT1, FcγRIIB, TNFAIP3, TRAF6, and TLR7. Based on B cell signaling literature and expression data, we proposed a role of BANK1 in B cells of tolerant patients that involved BCR, IP3R, and PLCG2, and a link with the apoptosis pathways. We confronted these data with our experiments on apoptosis in total B cells and Bregs, and this suggests different involvement for BANK1 in these two cells. Finally, we put in perspective our own data with other published data to hypothesize two different roles for BANK1 in B cells and in Bregs.

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Section: Discussionsupporting

confidence: 72%

Connection of BANK1, Tolerance, Regulatory B cells, and Apoptosis: Perspectives of a Reductionist Investigation

et al. 2021

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“…However, other cytokines can also contribute to Breg function, including TGF-b and IL-35. [10][11][12] In addition, TGF-b secretion by Bregs has been found to also play an important and independent role in immune regulation in various inflammatory diseases. 13 Studies examining the suppression of IL-17 + and IFN-c + T cells by B cells indicate that both IL-10and TGF-b-dependent processes are involved.…”

Section: Introductionmentioning

confidence: 99%

TGF‐β‐secreting regulatory B cells: unsung players in immune regulation

et al. 2021

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Regulatory B cells contribute to the regulation of immune responses in cancer, autoimmune disorders, allergic conditions and inflammatory diseases. Although most studies focus on regulatory B lymphocytes expressing interleukin-10, there is growing evidence that B cells producing transforming growth factor b (TGF-b) can also regulate T-cell immunity in inflammatory diseases and promote the emergence of regulatory T cells that contribute to the induction and maintenance of natural and induced immune tolerance. Most research on TGF-b + regulatory B cells has been conducted in models of allergy, cancer and autoimmune diseases, but there has, as yet, been limited scrutiny of their role in the transplant setting. Herein, we review recent investigations seeking to understand how TGF-b-producing B cells direct the immune response in various inflammatory diseases and whether these regulatory cells may have a role in fostering tolerance in transplantation.

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“…We have shown that human melanoma cells can induce both B cell receptor and CD40 signaling in activated B cells [ 3 ]. Among other mechanisms [ 30 ], the balance between B cell receptor and CD40 signaling in activated B cells critically determines the production of immunostimulatory vs. immunoinhibitory cytokines such as LTA vs. IL-10 (reviewed in [ 17 ]).…”

Section: Discussionmentioning

confidence: 99%

Loss of Lymphotoxin Alpha-Expressing Memory B Cells Correlates with Metastasis of Human Primary Melanoma

et al. 2021

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Activated antigen-experienced B cells play an unexpected complex role in anti-tumor immunity in human melanoma patients. However, correlative studies between B cell infiltration and tumor progression are limited by the lack of distinction between functional B cell subtypes. In this study, we examined a series of 59 primary and metastatic human cutaneous melanoma specimens with B cell infiltration. Using seven-color multiplex immunohistochemistry and automated tissue imaging and analysis, we analyzed the spatiotemporal dynamics of three major antigen-experienced B cell subpopulations expressing lymphotoxin alpha (LTA/TNFSF1) or interleukin-10 (IL-10) outside tertiary lymphoid structures. The expression of both LTA and IL-10 was not restricted to a particular B cell subtype. In primary melanomas, these cells were predominantly found at the invasive tumor-stroma front and, in metastatic melanomas, they were also found in the intratumoral stroma. In primary melanomas, decreased densities of LTA+ memory-like and, to a lesser extent, activated B cells were associated with metastasis. Compared with metastatic primary tumors, B cell infiltrates in melanoma metastases were enriched in both LTA+ memory-like and LTA+ activated B cells, but not in any of the IL-10+ B cell subpopulations. Melanoma disease progression shows distinct dynamics of functional B cell subpopulations, with the regulation of LTA+ B cell numbers being more significant than IL-10+ B cell subpopulations.

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IL-10-producing regulatory B cells and plasmocytes: Molecular mechanisms and disease relevance

Cited by 48 publications

References 94 publications

Connection of BANK1, Tolerance, Regulatory B cells, and Apoptosis: Perspectives of a Reductionist Investigation

Connection of BANK1, Tolerance, Regulatory B cells, and Apoptosis: Perspectives of a Reductionist Investigation

TGF‐β‐secreting regulatory B cells: unsung players in immune regulation

Loss of Lymphotoxin Alpha-Expressing Memory B Cells Correlates with Metastasis of Human Primary Melanoma

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