Abstract
Preterm birth (PTB) is defined as birth before 37 completed weeks of gestation. The causes of PTB are multiple and complex, the underlying pathophysiology being largely unknown. Interferences in the fine-tuned balance of the maternal immune system have been pointed to as one possible cause of PTB. Regulatory B cells (Breg) are part of the adaptive immune response, and recent data suggest that they may contribute to a healthy pregnancy by their regulatory/suppressive function.We investigated the frequency of Breg cells in peripheral blood of women undergoing PTB and control women immediately before giving birth via cesarean section. We detected an enhanced number of B cells, but a reduced number of Breg cells in women delivering preterm. In addition, the percentage of IL-10-producing B cells was decreased in PTB following stimulation with TLR agonists CpG or LPS, alone or combined with CD40L. This was associated with increased levels of pro-inflammatory cytokines in maternal serum. Moreover, isolated maternal B cells before delivering premature babies secreted higher level of the pro-inflammatory cytokine IL-6. No alterations in the frequency of regulatory T cells were found.Our data indicate that alterations in the number and function of Breg cells in peripheral maternal blood contribute to the immunological changes observed in preterm delivery and suggest these cells as important regulators of maternal immune responses.
Highlights
Preterm birth (PTB) is defined as the delivery of a baby before 37 completed weeks of gestation
We found that the number and function of B cells and Breg cells is disturbed in maternal blood immediately before the onset of PTB, further establishing an important role for B cells in a healthy pregnancy
We have recently shown that IL-10 and IL-10-producing Breg cells are important for fetal survival in a LPS-mediated mouse model of intrauterine fetal death [11]
Summary
Preterm birth (PTB) is defined as the delivery of a baby before 37 completed weeks of gestation. PTB is still a leading course for neonatal morbidity and mortality [1]. About 15 million babies and their mothers are affected every year with stable or even increasing frequencies. The PTB rate in Germany is one of the highest across Europe [2, 3]. PTB is a syndrome and has multiple etiologies. About one third of all PTBs in high-income countries are medically indicated/iatrogenic; the remaining approximately 70% are spontaneous [4]. PTB will be medically induced when the risk for the fetus or the mother outweighs the benefit to continue pregnancy, for example, in conditions such as preeclampsia or intrauterine growth
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