Marginal zone B cells emerge as a critical component of pregnancy well-being

Abstract

The success of eutherian mammal evolution was certainly supported by the ability of the already existing immune system to adapt to the presence of the semi-allogeneic fetus without losing the capability to defend the mother against infections. This required the acquisition of highly regulated and coordinated immunological mechanisms. Failures in the development of these strategies not only lead to the interruption of pregnancy but also compromise maternal health. Alongside changes on the cytokine profile -expansion of tolerogenic dendritic and regulatory T cells -a profound adaptation of the B cell compartment during pregnancy was recently described. Among others, the suppression of B cell lymphopoiesis and B cell lymphopenia were proposed to be protective mechanisms tending to reduce the occurrence of autoreactive B cells that might recognize fetal structures and put pregnancy on risk. On the other hand, expansion of the pre-activated marginal zone (MZ) B cell phenotype was described as a compensatory strategy launched to overcome B cell lymphopenia thus ensuring a proper defense. In this work, using an animal model of pregnancy disturbances, we demonstrated that the suppression of B cell lymphopoiesis as well as splenic B cell lymphopenia occur independently of pregnancy outcome. However, only animals undergoing normal pregnancies, but not those suffering from pregnancy disturbances, could induce an expansion and activation of the MZ B cells. Hence, our results clearly show that MZ B cells, probably due to the production of natural protective antibodies, participate in the fine balance of immune activation required for pregnancy well-being.

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

“…B cells can also be recruited by the chorioamniotic membranes [14] and constitute a portion of the choriodecidual leukocytes [16,57,58]. The role of B cells during pregnancy and its complications have been widely studied by Jensen and collaborators [59][60][61][62][63][64][65][66][67][68]. Taken together, these data provide further evidence that the adaptive limb of immunity is involved in the process of labor.…”

Progesterone and estradiol exert an inhibitory effect on the production of anti-inflammatory cytokine IL-10 by activated MZ B cells

“…Indeed, using a mouse model of pregnancy failures (Bobé et al, 1986) we could later confirm the crucial role of MZ B cells in pregnancy wellbeing by showing that pregnant mice developing normal pregnancies but not those suffering from pregnancy failures display an expansion of the MZ B cell compartment (Muzzio et al, 2016).…”

“…Hence they represent the first barrier against infections (Martin et al, 2001). In the context of pregnancy, we showed that MZ B cells numbers are increased in the spleen (Muzzio et al, 2014) and seems to be crucial for pregnancy wellbeing (Muzzio et al, 2016).…”

Characterization of the Highly Prevalent Regulatory CD24hiCD38hi B-Cell Population in Human Cord Blood

“…Their responses are mainly directed against encapsulated bacteria, including commensal microbiota (49–51). Marginal zone B-cells also play a role in normal pregnancy development (52), and it is known that antiencapsulated bacteria responses are lower in infants and young children (36). As TLRs activate Bregs (2, 3), the greater proportion of marginal zone-like B-cells observed might indicate increased cooperation in regulatory function after encapsulated bacterial stimulation.…”