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.
- Copyright © 2013 by The American Association of Immunologists, Inc.