B1 B cells acquire a proliferative and anti-inflammatory profile during pregnancy in mice

Abstract

B1 B cells are a distinct subpopulation of B cells characterized by their unique capacity of self-renewal and the ability to secrete IgM without foreign antigen exposure (natural antibodies). In addition, upon activation, B1 B cells produce large quantities of the potent anti-inflammatory cytokine IL-10. Though the mechanisms that control natural antibodies production are not fully elucidated, it was recently associated with a down-regulation of CD1d expression in B1 B cells. Taking into account that both, IL-10 and natural antibodies are known to be fundamental components in pregnancy wellbeing, the aim of this study was to evaluate proliferation status as well as CD1d expression and IL-10 production by B1 B cells during pregnancy. Flow cytometry analysis, on splenic B1 B cells from pregnant (P) and non-pregnant (NP) mice was performed to evaluate ki-67 (proliferation marker) and CD1d expression as well as IL-10 production upon LPS stimulation. We observed significantly higher expression levels of Ki-67 in splenic B1 B cells from P compared to NP (Unpaired t-test p<0,0001; n=3) mice which was mirrored by higher percentages of B1 B cells in the spleen of P mice (Unpaired t-test p=0,0095; n=11). In addition, B1 B cells from P mice expressed lower levels of CD1d as compared to NP mice (Unpaired t-test p<0,0001; n=3). Furthermore, LPS-stimulated B1 B cells from P mice produced significantly higher levels of IL-10 compared to NP mice in vitro (Unpaired t-test p=0,015; n=5).Overall, our results demonstrate that not only B1 B cells are expanded in the spleen during pregnancy but they also seem to acquire the capacity to produce higher levels of natural antibodies and IL-10 during this period, suggesting their critical role in the intricate process of pregnancy tolerance.