Abstract
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.
Highlights
Pregnancy in mammals is accompanied by profound changes and adaptations in the endocrine as well as the immune systems
It is known that women suffering from a pre-existing autoimmune disease demonstrate changes in disease expression during pregnancy and this has been associated with changes in female sex hormones
Once the embryo is implanted, trophoblast cells produce and secrete increasing levels of human chorionic gonadotropin, which on the one side stimulates the corpora lutea (CL) to continue producing progesterone, estradiol (E2), and estrone (E1) [1] and on the other side promotes angiogenesis in the uterine endothelium [2] as well as trophoblast migration and invasion into the uterine wall [3]. Besides these widely accepted functions of female sex hormones in coordinating and controlling anatomical modifications associated with gravity, abundant evidence has highlighted their role in shaping immune cells toward a transient state of tolerance necessary for the maintenance of pregnancy [4]
Summary
Pregnancy in mammals is accompanied by profound changes and adaptations in the endocrine as well as the immune systems. It is known that women suffering from a pre-existing autoimmune disease demonstrate changes in disease expression during pregnancy and this has been associated with changes in female sex hormones. Besides these widely accepted functions of female sex hormones in coordinating and controlling anatomical modifications associated with gravity, abundant evidence has highlighted their role in shaping immune cells toward a transient state of tolerance necessary for the maintenance of pregnancy [4].
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