# Understanding and harnessing the functions of B cells to prevent preterm labor

> **NIH NIH R21** · WAYNE STATE UNIVERSITY · 2020 · $192,500

## Abstract

Project Summary
 Premature birth (PTB) is estimated to affect 5–18% pregnancies worldwide. Despite extensive public health
efforts, PTL has remained an insidious and intractable cause of infant death and long-term illnesses, suggesting
that we do not completely understand PTL pathogenesis. Indeed, the prediction, prevention and treatment of PTL
have been very challenging. Intrauterine and systemic infection and/or inflammation are recognized
pathophysiologic mechanisms that account for 30–40% of PTL, and ~85% of spontaneous PTB cases at <28
weeks and ~65% of those before 37 weeks showed evidences of intrauterine inflammation. To this end, we have
focused on B cells, where our expertise lies, in pregnancy and PTL, because B cells are critical effectors and
regulators of innate and adaptive immunity that protects the host against infection, and B cell dysfunction crucially
contributes to many autoimmune and inflammatory conditions that predispose women to PTL. Our preliminary
studies showed that human choriodeciduas harbored B cells, but B cells in PTL choriodeciduas were functionally
altered. B cell-deficient mice were markedly more susceptible than wild-type (WT) mice to PTL after systemic
inflammation, but B cells conferred interleukin (IL)-10-independent protection against PTL. B cell deficiency in mice
diminished the level of uterine progesterone-induced blocking factor 1 (Pibf1), a progesterone-inducible molecule
that carries out many effector functions of progesterone in pregnancy. A lower serum and urine PIBF1
concentration in late pregnancy was strongly associated with an increased risk of PTL. More importantly,
therapeutic administration of PIBF1 mitigated PTL and uterine inflammation in B cell-deficient mice, and the
protective activity resided in the amino (N) terminal part of PIBF1 (nPIBF1). Interestingly, PIBF1 expression by
uterine B cells in late gestation was dependent on the mucosal alarmin IL-33, and PTL patients had diminished
expression of the α-chain of IL-33 receptor, ST2L, on choriodecidual B cells and a lower level of active PIBF1 in late
gestation choriodecidua. However, the mechanisms by which PIBF1 protects against PTL and the causes of the
intriguing B cell defect in PTL are unknown. As we work to develop PIBF1 into a therapeutic agent to prevent PTL,
we want to know the answers to these key questions. Employing computational modelling, biochemical methods
and mouse models, studies in Aim 1 will determine the mechanism of PIBF1-mediated protection against PTL.
Studies in Aim 2 will use molecular and biochemical approaches to determine the causes of the diminished IL-33Rα
expression that underlies the functional defects of B cell in PTL patients. Our studies will not only catalyze the
preclinical and clinical development of nPIBF1 as a therapeutic agent to prevent or treat PTL, but also offer novel
and specific targets to predict and mitigate the B cell defects in this prevalent, devastating and intractable condition.
Be...

## Key facts

- **NIH application ID:** 9880394
- **Project number:** 5R21AI138089-02
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Kang Chen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880394

## Citation

> US National Institutes of Health, RePORTER application 9880394, Understanding and harnessing the functions of B cells to prevent preterm labor (5R21AI138089-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9880394. Licensed CC0.

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