Maternal and fetal mechanisms of B cell regulation during pregnancy: human Chorionic Gonadotropin stimulates B cells to produce IL-10 while alphafetoprotein drives them into apoptosis

FRANZISKA FETTKE; ANNE SCHUMACHER; ANDREA CANELLADA; NATALIA TOLEDO; ISABELLE BEKEREDJIAN-DING; ALBERT BONDT; MANFRED WUHRER; SERBAN D. COSTA; ANA C. ZENCLUSSEN

Frontiers in Immunology

Frontiers.org

Año: 2016

Maternal immune tolerance towards the fetus is an essential requisite for pregnancy. While T cell functions are well documented,little is known about the participation of B cells. We have previously suggested that IL-10 producing B cells are involved inpregnancy tolerance in mice and humans. By employing murine and human systems, we report now that fetal trophoblastspositively regulate the generation of IL-10 producing B cells. We next studied the participation of hormones produced by theplacenta as well as the fetal protein alpha-fetoprotein (AFP) in B cell modulation. Human Chorionic Gonadotropin (hCG), but notprogesterone, estrogen or a combination of both, was able to promote changes in B cell phenotype and boost their IL-10production, which was abolished after blocking hCG. The hCG-induced B cell phenotype was not associated with augmentedgalactosylation, sialylation or fucosylation of IgG subclasses in their Fc. In vitro, hCG induced the synthesis of asymmetricallyglycosylated antibodies. Interestingly, AFP had dual effects depending on the concentration. At concentrations corresponding tomaternal serum levels, it did not modify the phenotype or IL-10 secretion of B cells. At fetal concentrations, however, AFP was ableto drive B cells into apoptosis, which may indicate a protective mechanism to avoid maternal B cells to reach the fetus.Our data suggests that the fetus secrete factors that promote a pregnancy-friendly B cell phenotype, unraveling interestingaspects of B cell function and modulation by pregnancy hormones and fetal proteins.