Clusters of Tolerogenic B Cells Feature in the Dynamic Immunological Landscape of the Pregnant Uterus

Benner, Marilen; Feyaerts, Dorien; García, Celia Cartagena; İnci, Nurcan; López, Sergi Cedó; Fasse, Esther; Shadmanfar, Wijs; Heijden, Olivier W.H. van der; Gorris, Mark A.J.; Joosten, Irma; Ferwerda, Gerben; Molen, Renate G. van der

doi:10.1016/j.celrep.2020.108204

Cited by 23 publications

(22 citation statements)

References 63 publications

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“…This high B cell-derived IL-10 expression was later associated with a decreased expression of CD86 and an increased CD40 activation by recipient T cells ( 209 , 280 ). Besides allograft tolerance, mounting evidence implicates IL-10 + B cells in mechanisms governing tolerance to semi-allogeneic fetus during pregnancy in both mouse ( 147 , 281 – 285 ) and human ( 146 , 147 , 286 – 289 ), which include the generation of tolerogenic DCs and Tregs and a reduction in Th17 cells ( 281 , 282 , 290 ).…”

Section: Suppressive Mechanisms Of Bregs By Soluble Moleculesmentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory B Cells

et al. 2021

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Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.

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Section: Suppressive Mechanisms Of Bregs By Soluble Moleculesmentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory B Cells

et al. 2021

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“…B cells, and their production of immune modulatory cytokines and antibodies, are also dynamically regulated during pregnancy with potentially beneficial or detrimental impacts (56). Progressively increased accumulation of clustered CD27+IgD-switched memory CD19+ B cells and plasmablasts are found at the maternal-fetal interface during human pregnancy (57). These decidual B cells lie in close approximation to FOXP3+ regulatory T cells, selectively produce IL-10, and are phenotypically distinct from circulating B cellshighlighting the potential for cross-talk between these adaptive immune cell types in sustaining fetal tolerance (57,58).…”

Section: Maternal Innate and Adaptive Immune Cells With Fetal Specificitymentioning

confidence: 99%

“…Progressively increased accumulation of clustered CD27+IgD-switched memory CD19+ B cells and plasmablasts are found at the maternal-fetal interface during human pregnancy (57). These decidual B cells lie in close approximation to FOXP3+ regulatory T cells, selectively produce IL-10, and are phenotypically distinct from circulating B cellshighlighting the potential for cross-talk between these adaptive immune cell types in sustaining fetal tolerance (57,58). With regards to parity, pregnancy-induced humoral sensitization has long been recognized.…”

Section: Maternal Innate and Adaptive Immune Cells With Fetal Specificitymentioning

confidence: 99%

Epidemiology of Pregnancy Complications Through the Lens of Immunological Memory

et al. 2021

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In the fifteen minutes it takes to read this short commentary, more than 400 babies will have been born too early, another 300 expecting mothers will develop preeclampsia, and 75 unborn third trimester fetuses will have died in utero (stillbirth). Given the lack of meaningful progress in understanding the physiological changes that occur to allow a healthy, full term pregnancy, it is perhaps not surprising that effective therapies against these great obstetrical syndromes that include prematurity, preeclampsia, and stillbirth remain elusive. Meanwhile, pregnancy complications remain the leading cause of infant and childhood mortality under age five. Does it have to be this way? What more can we collectively, as a biomedical community, or individually, as clinicians who care for women and newborn babies at high risk for pregnancy complications, do to protect individuals in these extremely vulnerable developmental windows? The problem of pregnancy complications and neonatal mortality is extraordinarily complex, with multiple unique, but complementary perspectives from scientific, epidemiological and public health viewpoints. Herein, we discuss the epidemiology of pregnancy complications, focusing on how the outcome of prior pregnancy impacts the risk of complication in the next pregnancy — and how the fundamental immunological principle of memory may promote this adaptive response.

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“…Given the importance of follicular structures in the genesis of antibody-secreting cells (discussed further below), these data suggest that anti-HLA antibody from antibody-secreting cells is unlikely to be generated in the uterus. Furthermore, in vitro analyses of decidual B cells versus peripheral B cells demonstrate an augmented ability to produce the immunoregulatory cytokine, IL-10, in the presence or absence of co-stimulatory signals ( 27 ). These data therefore suggest that the uterus may comprise a specialized tissue-resident B cell population with an as yet undetermined interaction with uterine T cells.…”

Section: Overview Of the Anatomy Of Pregnancy Sensitization And The Availability Of Fetal Alloantigenmentioning

confidence: 99%

Memory B Cells in Pregnancy Sensitization

2021

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Memory B cells play an important role in immunity to pathogens as these cells are poised to rapidly differentiate into antibody-secreting cells upon antigen re-encounter. Memory B cells also develop over the course of HLA-sensitization during pregnancy and transplantation. In this review, we discuss the potential contribution of memory B cells to pregnancy sensitization as well as the impact of these cells on transplant candidacy and outcomes. We start by summarizing how B cell subsets are altered in pregnancy and discuss what is known about HLA-specific B cell responses given our current understanding of fetal antigen availability in maternal secondary lymphoid tissues. We then review the molecular mechanisms governing the generation and maintenance of memory B cells during infection – including the role of T follicular helper cells - and discuss the experimental evidence for the development of these cells during pregnancy. Finally, we discuss how memory B cells impact access to transplantation and transplant outcomes for a range of transplant recipients.

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Clusters of Tolerogenic B Cells Feature in the Dynamic Immunological Landscape of the Pregnant Uterus

Cited by 23 publications

References 63 publications

Immunosuppressive Mechanisms of Regulatory B Cells

Immunosuppressive Mechanisms of Regulatory B Cells

Epidemiology of Pregnancy Complications Through the Lens of Immunological Memory

Memory B Cells in Pregnancy Sensitization

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