Regulatory B cells, A to Z

Jansen, Kirstin; Cevhertas, Lacin; Ma, Siyuan; Satitsuksanoa, Pattraporn; Akdiş, Mübeccel; Veen, Willem van de

doi:10.1111/all.14763

Cited by 84 publications

(74 citation statements)

References 157 publications

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“…However, in our cohort of patients, we did not find an association between parasitemia and the frequency of B10 cells or IL-10 secretion levels in B cell culture supernatants, suggesting that other cell types are the source of IL-10 in chronic T. cruzi infection. In fact, as it was mentioned before, a negative correlation between parasite detection in blood and the percentage of CD24 high CD27 + B cell exists in CCD patients, and this subset is identified as the central IL-10 secreting B cells in humans (Jansen et al, 2021).…”

Section: Discussionmentioning

confidence: 57%

“…Furthermore, CD19 + CD24 high CD38 high Breg represents a high percentage of the bulk of B lymphocyte in cord and peripheral blood of healthy neonate and was found increased in late-onset sepsis, linking these cells with pregnancy success (Li et al, 2018). On the other hand, CD19 + CD24 high CD27 + B cell subset harnesses its immunomodulatory activity mostly by regulating the production of pro-inflammatory cytokines, tumor necrosis factor (TNF)-a in monocytes and interferon (IFN)-g in CD4 + T cells (Iwata et al, 2011;Hasan et al, 2019;Jansen et al, 2021). Alterations in the frequency of this memory-like Breg have been detected in similar scenarios than the CD19 + CD24 high CD38 high Breg, including cancer (Abebe et al, 2021;Jansen et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, CD19 + CD24 high CD27 + B cell subset harnesses its immunomodulatory activity mostly by regulating the production of pro-inflammatory cytokines, tumor necrosis factor (TNF)-a in monocytes and interferon (IFN)-g in CD4 + T cells (Iwata et al, 2011;Hasan et al, 2019;Jansen et al, 2021). Alterations in the frequency of this memory-like Breg have been detected in similar scenarios than the CD19 + CD24 high CD38 high Breg, including cancer (Abebe et al, 2021;Jansen et al, 2021). However, and depending on the different disease models, stimulation conditions as well as the panel of cell surface markers used in the flow cytometry analysis, other B cells are also classified as Breg.…”

Section: Introductionmentioning

confidence: 99%

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Trypanosoma cruzi Induces Regulatory B Cell Alterations in Patients With Chronic Chagas Disease

Girard

Ossowski

Muñoz-Calderón

et al. 2021

Front. Cell. Infect. Microbiol.

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The clinical evolution of patients with chronic Chagas disease (CCD) is mainly associated with an excessive inflammation and a defective immunomodulatory profile caused by the interaction between T. cruzi and the host. Regulatory B (Breg) cells exert immune suppression mostly through IL-10 production (B10 cells), but also through IL-10-independent mechanisms. Previously, we demonstrated that CCD patients with cardiomyopathy show changes in the ex vivo Breg cell phenotypic distribution although maintain IL-10 production capacity. Here, we sought to identify potential alterations on Breg cells upon in vitro stimulation. Isolated B cells from CCD patients with or without cardiomyopathy and non-infected (NI) donors were stimulated with T. cruzi lysate or CpG + CD40L, and characterized by flow cytometry based on the expression of CD24, CD27, CD38, and the regulatory molecules IL-10 and PD-L1. IL-10 and IL-17 secretion in the supernatant of B cells was evaluated by ELISA. Data showed that T. cruzi stimulation diminished the expression of CD24 and CD38 on CD27− B cells while reducing the percentage of CD24high inside CD27+ B cells. Furthermore, T. cruzi induced a regulatory B cell phenotype by increasing B10 cells and IL-10 secretion in all the groups. The innate-like B10 cells expansion observed in patients with cardiomyopathy would be associated with CD27− B10 cell subsets, while no predominant phenotype was found in the other groups. Patients with cardiomyopathy also displayed higher IL-17 secretion levels in T. cruzi–activated B cells. CpG + CD40L stimulation revealed that B cells from CCD patients and NI donors had the same ability to differentiate into B10 cells and secrete IL-10 in vitro. Additionally, CCD patients showed an increased frequency of CD24−CD27− B cells and a reduction in the percentage of CD24highCD27+ Breg cells, which appeared to be inversely correlated with the presence of T. cruzi DNA in blood. Finally, CCD patients exhibited a higher frequency of PD-L1+ B cells in T. cruzi–stimulated samples, suggesting that IL-10-independent mechanisms could also be tangled in the control of inflammation. Altogether, our results provide evidence about the potential role of Breg cells in the immune response developed against T. cruzi and its contribution to chronic Chagas cardiomyopathy.

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Trypanosoma cruzi Induces Regulatory B Cell Alterations in Patients With Chronic Chagas Disease

Girard

Ossowski

Muñoz-Calderón

et al. 2021

Front. Cell. Infect. Microbiol.

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“… 122 Regulatory B cells suppress the activity of effector T cells and promote Treg cell differentiation primarily via IL-10. 123 , 124 However, they can secrete other soluble molecules with regulatory roles (TGF-β, IL-35, TSP-1, IDO, etc.) and express surface-bound molecules that enable immunosuppressive cellular interactions (PD-1, FASL, CD73, CD9, CD1d, etc.).…”

Section: Memory Reconstitution Of Allergymentioning

confidence: 99%

Memory Generation and Re-Activation in Food Allergy

Koenig

Bruton

Phelps

et al. 2021

ITT

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Recent evidence has highlighted the critical role of memory cells in maintaining lifelong food allergies, thereby identifying these cells as therapeutic targets. IgG + memory B cells replenish pools of IgE-secreting cells upon allergen exposure, which contract thereafter due to the short lifespan of tightly regulated IgE-expressing cells. Advances in the detection and highly dimensional analysis of allergen-specific B and T cells from allergic patients have provided insight on their phenotype and function. The newly identified Th2A and Tfh13 populations represent a leap in our understanding of allergen-specific T cell phenotypes, although how these populations contribute to IgE memory responses remains poorly understood. Within, we discuss the mechanisms by which memory B and T cells are activated, integrating knowledge from human systems and fundamental research. We then focus on memory reactivation, specifically, on the pathways of secondary IgE responses. Throughout, we identify areas of future research which will help identify immunotargets for a transformative therapy for food allergy.

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“…B cells also regulate immune responses independent of IL‐10 through expression of TGFβ, IL‐35, IgM, PDL‐1, FasL, and adenosine (reviewed in refs. 4,5). Recently, it has been recognized that many of the suppressive functions of regulatory B lineage cells are exerted by antibody‐secreting cells (ASCs), plasmablasts and plasma cells, that secrete both antibodies and the immunosuppressive cytokines IL‐10 or IL‐35.…”

Section: Introductionmentioning

confidence: 99%

Immunoregulation by antibody secreting cells in inflammation, infection, and cancer

McGettigan

Debes

2021

Immunological Reviews

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Antibody‐secreting cells (ASCs) are considered work horses of the humoral immune response for their tireless effort to produce large amounts of antibodies that fulfill an array of functions in host defense, inflammation, and maintenance of homeostasis. While traditionally considered largely senescent cells, surprising recent findings demonstrate that subsets of ASCs downmodulate ongoing immune responses independent of antibody formation. Such regulatory ASCs produce IL‐10 or IL‐35 and are implicated in maintaining tissue and immune homeostasis. They also serve to suppress pathogenic leukocytes in infection, allergy, and inflammatory diseases that affect tissues, such as the central nervous system and the respiratory tract. Additionally, regulatory ASCs infiltrate various cancer types and restrict effective anti‐tumor T cell responses. While incompletely understood, there is significant overlap in factors that control ASC differentiation, IL‐10 expression by B cells and the generation of ASCs that secrete both antibodies and IL‐10. In this review, we will cover the biology, phenotype, generation, maintenance and function of regulatory ASCs in various tissues under pathological and steady states. An improved understanding of the development of regulatory ASCs and their biological roles will be critical for generating novel ASC‐targeted therapies for the treatment of inflammatory diseases, infection, and cancer.

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Regulatory B cells, A to Z

Cited by 84 publications

References 157 publications

Trypanosoma cruzi Induces Regulatory B Cell Alterations in Patients With Chronic Chagas Disease

Trypanosoma cruzi Induces Regulatory B Cell Alterations in Patients With Chronic Chagas Disease

Memory Generation and Re-Activation in Food Allergy

Immunoregulation by antibody secreting cells in inflammation, infection, and cancer

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