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.
Caucheteux
Stéphane M
SM
Laboratory of Immune Regulations and Development, Department of Developmental Biology, Institut J. Monod, (CNRS and Universitities Paris 6 and 7), Paris, France.
Gendron
Marie-Claude
MC
Kanellopoulos-Langevin
Colette
C
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005260:Female; D007075:Immunoglobulin M / Q000276:immunology; D051917:Leukosialin; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D012795:Sialoglycoproteins / Q000032:analysis / Q000378:metabolism; D015533:Transcriptional Activation; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D007075:Immunoglobulin M; D051917:Leukosialin; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D019014:fas Receptor; C052617:Bcl2 protein, mouse