B-1a B cells regulate T cell differentiation associated with pregnancy disturbances.

DURING PREGNANCY, THE MATERNAL IMMUNE SYSTEM FACES A DOUBLE DILEMMA: tolerate the growing semi-allogeneic fetus and at the same time protect the mother and the progeny against pathogens. This requires a fine and extremely regulated equilibrium between immune activation and tolerance. As professional antigen presenting cells, B cells and in particular B-1a B cells, can activate or tolerize T cells and thus participate in the generation or regulation of the immune response. B-1a B cells were involved in the humoral immune response leading to pre-eclampsia, one of the main medical complications during pregnancy. Here we demonstrated that B-1a B cells are additionally involved in cellular immune mechanisms associated with pregnancy complications. Using a mouse model of pregnancy disturbances, we showed that B-1a B cells from animals suffering pregnancy disturbances but not from those developing normal pregnancies induce the differentiation of naïve T cells into Th17 and Th1 cells. This differential role of B-1a B cells during pregnancy seems to be associated with the co-stimulatory molecule CD86 as normal pregnant mice showed lower percentages of CD86 expressing B-1a B cells as compared to pregnant mice developing pregnancy disturbances or to non-pregnant animals. Our data bring to light a new and not explored role of B-1a B cells in the context of pregnancy.

Cutting edge: IL-10-producing regulatory B cells in early human pregnancy.

PROBLEM: The function of IL-10 producing regulatory B cells (Breg) during gestation is unknown. Here, we aimed to understand their participation in early pregnancy. METHOD: CD19(+) CD24(hi) CD27(+) B cell frequency, measured by flow cytometry, increased with pregnancy onset but not in the case of spontaneous abortions. RESULTS: B cells from non-pregnant women cultured with serum from normal pregnant women produced higher IL-10 levels than those cultured with serum from spontaneous abortion patients or autologous serum. CD19(+) -activated B cells from pregnant women strongly suppressed TNF-a production by CD4(+) T cells when cocultured. We identified hCG as an important factor regulating the number and function of Breg during pregnancy. CONCLUSIONS: Breg emerge as important players in pregnancy; they suppress undesired immune responses from maternal T cells and are therefore important for tolerance acquisition.