Editors' ChoiceReproductive Biology

B cells prevent preterm labor

See allHide authors and affiliations

Science Signaling  17 Jan 2017:
Vol. 10, Issue 462, eaam7592
DOI: 10.1126/scisignal.aam7592

Premature labor and consequent neonatal mortality may be prevented by stimulating the expression of PIBF1 in uterine B cells.

Systemic infection and inflammation can cause premature (“preterm”) labor before 37 weeks of gestation, and preterm birth is a leading cause of neonatal mortality worldwide. B cells combat infection and suppress inflammation by producing antibodies and interleukin-10 (IL-10), respectively, and maternal B cells are substantially modified during pregnancy, presumably to avoid rejection of the semi-allogeneic fetus. B cell dysfunction is associated with pregnancy complications, including preterm labor. Huang et al. isolated and characterized B cells from the choriodecidual stroma (a part of the uterine lining) obtained from women undergoing term or preterm labor. Preterm samples had a greater number and activation of B cells and supposed “B-1” cells, which can secrete auto- and polyreactive immunoglobulin, and preterm choriodecidual epithelial/stromal tissue was enriched in several B cell–stimulating molecules. However, in a mouse model of systemic inflammation–induced preterm labor using lipopolysaccharide (LPS) as the inflammatory stimulus, B cell deficiency promoted uterine inflammation and a higher incidence of preterm labor and neonatal mortality, indicating that B cells protected against preterm labor. The hormone progesterone promotes full-term pregnancy, and isoforms of the immunomodulatory protein progesterone-induced blocking factor 1 (PIBF1) are secreted by immune cells and trophoblasts during pregnancy. Various immunoassays revealed that human choriodecidual B cells are abundant in PIBF1 during late gestation. B cell–deficient mice had lower basal and LPS-induced expression of Pibf1 in late gestation uterine tissue but similar serum progesterone concentrations when compared with wild-type mice. LPS-induced Pibf1 expression was restored through adoptive B cell transfer, and administration of recombinant full-length (but not a C-terminal fragment of) human PIBF1 to B cell–deficient mice decreased LPS-induced uterine inflammation and preterm labor and delivery and neonatal mortality. A cytokine screen in human peripheral B cells revealed that IL33 promoted PIBF1 expression; uterine B cells from Il33−/− mice at late gestation had decreased expression of Pibf1. IL-33 is a “danger signal” indicating tissue damage; however, preterm human choriodecidual B cells had reduced abundance of both the IL-33 receptor α-chain and PIBF1, indicating that despite being greater in number and activation, diminished reception of the IL-33 danger signal and thus reduced induction of PIBF1 prevents B cells from mounting a protective response to inflammation during late pregnancy. The study reveals new therapeutic avenues to explore for patients at risk of premature labor.

Highlighted Article

View Abstract

Stay Connected to Science Signaling

Navigate This Article