Maternal B cell signaling orchestrates fetal development in mice

Mandy, Busse, Stefanie, Langwisch, Kerry, Tedford, Klaus-Dieter, Fischer, Ana Claudia, Zenclussen

Development |

B cell participation in early embryo/fetal development and the underlying molecular pathways have not been explored. To understand whether maternal B cell absence or impaired signaling interferes with placental and fetal growth, we paired CD19-deficient (CD19−/−) mice, females with B cell-specific MyD88 (BMyD88−/−) or IL10 (BIL10−/−) deficiency as well as wild-type and MyD88−/− controls on C57Bl/6 background with BALB/c males. Pregnancies were followed by ultrasound and Doppler measurements. Implantation number was reduced in BMyD88−/− and MyD88−/− mice. Loss of MyD88 or B cell-specific deletion of MyD88 or IL10 resulted in decreased implantation areas at gestational day (gd) 5, gd8 and gd10, accompanied by reduced placental thickness, diameter and areas at gd10. Uterine artery resistance was enhanced in BIL10−/− dams at gd10. Challenge with 0.4 mg lipopolysaccharide/kg bodyweight at gd16 revealed that BMyD88−/−, BIL10−/− and CD19−/− mothers delivered preterm, whereas controls maintained their pregnancy. B cell-specific MyD88 and IL10 expression is essential for appropriate in utero development. IL10+B cells are involved in uterine blood flow regulation during pregnancy. Finally, B cell-specific CD19, MyD88 and IL10 expression influences susceptibility towards preterm birth.