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- Klinik und Poliklinik für Frauenheilkunde u. Geburtshilfe (3) (remove)
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- Frontiers Media S.A. (3) (remove)
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.
For the normal development of pregnancy, a balance between immune tolerance and defense is crucial. However, the mechanisms mediating such a balance are not fully understood. CD83 is a transmembrane protein whose expression has been linked to anti-inflammatory functions of T and B cells. The soluble form of CD83, released by cleavage of the membrane-bound protein, has strong anti-inflammatory properties and was successfully tested in different mouse models. It is assumed that this molecule contributes to the establishment of immune tolerance. Therefore, we postulated that the expression of CD83 is crucial for immune tolerance during pregnancy in mice. Here, we demonstrated that the membrane-bound form of CD83 was upregulated in T and B cells during allogeneic murine pregnancies. An upregulation was also evident in the main splenic B cell subtypes: marginal zone, follicular zone, and transitional B cells. We also showed that there was an augmentation in the number of CD83+ cells toward the end of pregnancy within splenic B and CD4+ T cells, while CD83+ dendritic cells were reduced in spleen and inguinal lymph nodes of pregnant mice. Additionally, B lymphocytes in late-pregnancy presented a markedly higher sensitivity to LPS in terms of CD83 expression and sCD83 release. Progesterone induced a dosis-dependent upregulation of CD83 on T cells. Our data suggest that the regulation of CD83 expression represents a novel pathway of fetal tolerance and protection against inflammatory threats during pregnancy.
The Role of Pregnancy-Associated Hormones in the Development and Function of Regulatory B Cells
(2014)
During mammalian pregnancy, highly specialized mechanisms of immune tolerance are triggered in order to allow the semi-allogeneic fetus to grow within the maternal uterus in harmony with the maternal immune system. Among other mechanisms, changes in the endocrine status have been proposed to be at least part of the machinery responsible for the induction of immune tolerance during pregnancy. Indeed, pregnancy-associated hormones, estradiol, progesterone, and human chorionic gonadotropin are known to confer immune suppressive capacity to innate as well as adaptive immune cells. Regulatory B cells, a subpopulation of B lymphocytes with strong immunosuppressive functions, were shown to expand during pregnancy. Furthermore, it is well-known that some women suffering from multiple sclerosis, significantly improve their symptoms during pregnancy and this was attributed to the effect of female sex hormones. Accordingly, estradiol protects mice from developing experimental autoimmune encephalomyelitis by triggering the expansion and activation of regulatory B cells. In this review, we discuss different mechanisms associated with the development, activation, and function of regulatory B cells with a special focus on those involving pregnancy-associated hormones.