Defective induction of regulatory B cells by decidua stromal cells underlies the pathogenesis of preterm birth

Abstract Preterm birth is the leading cause of mortality and morbidity of newborns. Many maternal autoimmune conditions that predispose to preterm birth involve the dysregulation of autoreactive B cells that contribute to disease pathogenesis. Despite the fundamental roles of B cells as effectors and regulators of immunity, their functions in pregnancy are poorly understood. We found that human B cells undergo activation, class switching, memory and plasmacytoid differentiation in the decidua in situ. Preterm decidua harbors increased numbers of total B cells and B-1 cells but diminished numbers of IL-10-producing regulatory B cells in vivo. Furthermore, stromal cells in preterm decidua, as compared to those in term decidua, stimulate increased B cell activation and the differentiation of potentially autoreactive B cells, but are defective in inducing IL-10 expression by B cells. These results demonstrate that preterm birth involves abnormal B cell functions at the maternal-fetal interface, whereby decidua stromal dysfunction engenders unique populations of B cells with increased autoreactivity but diminished regulatory functions, and suggest that regulatory B cells are important for the maintenance of normal pregnancy. These studies provide insights into the functions of B cells at the maternal-fetal interface during pregnancy and inform the design of B cell-targeted therapies to treat preterm birth and other pregnancy complications involving B cell dysfunction.