Lymphoid Aggregates of Tolerogenic B Cells Feature in the Dynamic Immunological Landscape of the Uterus from Pre-Pregnancy to Delivery

Abstract

Well-timed interaction of correctly functioning maternal immune cells is essential to facilitate healthy placenta formation, as the uterine immune environment has to tolerate the semi-allogeneic fetus, and allow for adequate trophoblast invasion. Here, we assessed the uterine immune signature before and during pregnancy. Extensive supervised and unsupervised flow cytometry clustering strategies not only showed a general increase in immune memory throughout pregnancy, but also revealed continuous presence of B cells. Contrary to the belief that B cells are merely a pathological consequence in decidua, decidual B cells produced IL-10 and were found to be localized in lymphocyte aggregates, together with FOXP3+ T cells. These decidual B cells might have the ability to modify the local immune environment at the fetal-maternal interface by prohibiting extensive inflammation, e.g. by the induction of regulatory T cells. Our findings therefore highlight an as yet undisclosed role for B cells in healthy placentation.