Preterm birth (PTB) is a leading cause of neonatal death worldwide1. Intrauterine and systemic infection and inflammation cause 30–40% of spontaneous preterm labor (PTL)2, which precedes PTB. Although antibody production is a major immune defense mechanism against infection, and B cell dysfunction has been implicated in pregnancy complications associated with PTL3,4, the functions of B cells in pregnancy are not well known5–8. We found that choriodecidua of women undergoing spontaneous PTL harbored functionally altered B cell populations. B cell–deficient mice were markedly more susceptible than wild-type (WT) mice to PTL after inflammation, but B cells conferred interleukin (IL)-10-independent protection against PTL. B cell deficiency in mice resulted in a lower uterine level of active progesterone-induced blocking factor 1 (PIBF1), and therapeutic administration of PIBF1 mitigated PTL and uterine inflammation in B cell–deficient mice. B cells are a significant producer of PIBF1 in human choriodecidua and mouse uterus in late gestation. PIBF1 expression by B cells is induced by the mucosal alarmin IL-33 (ref. 9). Human PTL was associated with diminished expression of the a-chain of IL-33 receptor on choriodecidual B cells and a lower level of active PIBF1 in late gestation choriodecidua. These results define a vital regulatory cascade involving IL-33, decidual B cells and PIBF1 in safeguarding term pregnancy and suggest new therapeutic approaches based on IL-33 and PIBF1 to prevent human PTL.

To tackle the scientific challenges of maternal vaccination and to provide the public with informed vaccination choices, scientists and clinicians in different disciplines must work closely and have a mechanistic understanding of the systemic, reproductive and mammary mucosal immune responses to vaccines. The use of animal models should be coupled with human studies in an iterative manner for maternal vaccine experimentation, evaluation and optimization. Systems biology approaches should be adopted to improve the speed, accuracy and safety of maternal vaccine targeting.