Abstract

A successful outcome to pregnancy is dependent on the ability of the maternal uterine microenvironment to regulate inflammation processes and establish maternal tolerance. Recently, B cells have been shown to influence pregnancy outcomes as aberrations in their numbers and functions are associated with obstetric complications. In this study, we aimed to comprehensively examine the population frequency and phenotypic profile of B cells over the course of murine pregnancy. Our results demonstrated a significant expansion in B cells within the uterus during the peri-implantation period, accompanied by alterations in B cell phenotype. Functional evaluation of uterine B cells purified from pregnant mice at day 5.5 post-coitus established their regulatory capacity as evidenced by effective suppression of proliferation and activation of syngeneic CD4+ T cells. Flow cytometric analysis revealed that the uterine B cell population has an expanded pool of IL-10-producing B cells bearing upregulated expression of co-stimulatory molecules CD80 and CD86 and activation marker CD27. Our investigations herein demonstrate that during the critical stages surrounding implantation, uterine B cells are amplified and phenotypically modified to act in a regulatory manner that potentially contributes toward the establishment of maternal immunological tolerance in early pregnancy.

Highlights

  • Pregnancy is a model of immune tolerance wherein the mother carries a semi-allogeneic fetus that in principle triggers a maternal immune response due to the presence of paternally derived fetal alloantigens; the inflammation is kept at a tolerable level and the pregnancy progresses

  • Our results indicate that these uterine B cells undergo changes in frequency and phenotype, during the peri-implantation phase of pregnancy between days 2.5 and 8.5 post-coitus

  • We show in ex vivo experiments that uterine B cells collected from pregnant females at day 5.5 pc significantly suppressed proliferation and activation of syngeneic CD4+ T cells via cell-cell interactions

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Summary

Introduction

Pregnancy is a model of immune tolerance wherein the mother carries a semi-allogeneic fetus that in principle triggers a maternal immune response due to the presence of paternally derived fetal alloantigens; the inflammation is kept at a tolerable level and the pregnancy progresses. In early pregnancy, it is well-accepted that for implantation to occur, a regulated pro-inflammatory microenvironment that permits tissue remodeling and angiogenesis at the maternal-fetal interface is required. For B cells, their role in the induction of maternal immune tolerance in pregnancy to date remains poorly understood

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