Pregnancy-induced alterations of B cell maturation and survival are differentially affected by Fas and Bcl-2, independently of BcR expression.

In the present work, we have analyzed the roles of two molecules involved in the regulation of cell survival, Bcl2 and Fas, in the pregnancy-induced down-regulation of B lymphopoiesis in mice. Our results show that the overexpression of the anti-apoptotic molecule Bcl2 in Bcl2-transgenic (Tg) B cells is able to protect 'D' fraction pre-B cells from pregnancy-induced deletion. In contrast, in Fas(lpr/lpr) mice bearing a mutated cell death receptor Fas, such B cell targets are not protected. Moreover, bone marrow B cell sub-populations at both ends of the differentiation pathway, i.e. pre-pro 'A' and mature 'E-F' fraction B cells, which are not the major targets of the pregnancy-induced down-regulation, are doubled during pregnancy in Fas(lpr/lpr) mice only. Altogether, these data strongly suggest that B cell down-regulation during pregnancy is due to apoptotic events blocked by Bcl2, but does not depend on a functional Fas receptor. The expression of a transgenic BcR in the 3-83mudelta BcR-Tg mouse model yields similar observations, which indicates that early BcR expression does not alter bone marrow B cell fates during pregnancy.