title: B-lymphopoiesis gains sensitivity to subsequent inhibition by estrogens during final phase of fetal development.
abstract: Adult B-lymphopoiesis is suppressed by the inhibitory effects of elevated estrogens during pregnancy. At the same time, hematopoietic cells in the fetal liver are resistant to this suppression by estrogens and ensure active production of B-cells. We investigated whether this unresponsiveness to estrogens of fetal cells also applies to cells obtained from a newborn liver and projects into the adult hematopoiesis when fetal liver cells are transplanted to adult mice. Mixtures of fetal liver (E14.5), neonatal liver (P0.5) and adult bone marrow (BM) cells were co-transplanted into adult primary and secondary recipients treated with high doses of estrogen in the Ly5.1/Ly5.2 congenic mouse model. Total chimerism as a proportion of all nucleated blood cells, chimerism as a proportion of B220+ B-cells, and of other blood cell lineages as well, were determined by flow cytometry. B-lymphopoiesis derived from fetal liver (E14.5) stem cells remained resistant to estrogen after transplantation into both primary and secondary adult recipients, for up to 280 days. In contrast, B-lymphopoiesis derived from neonatal liver (P0.5) stem cells was resistant to estrogen only for approximately 50 days after the primary transplantation to the adult BM microenvironment. These results provide further evidence for a critical developmental period of B-lymphopoiesis during its fetal liver stage. In the mouse, critical developmental events that allow for the subsequent expressed sensitivity of B-lymphopoiesis for suppression by estrogens after sexual maturation appear to occur during the period of late-stage fetal liver hematopoiesis before its migration to the bone marrow.
authors.affiliation: Institute of Pathophysiology and Center of Experimental Hematology, Charles University in Prague, First Faculty of Medicine, Praha, Czech Republic. peliskat@hotmail.com
authors.forename: Tereza
authors.initials: T
authors.lastname: Hlobeňová
authors.forename: Luděk
authors.initials: L
authors.lastname: Sefc
authors.forename: Ko-Tung
authors.initials: KT
authors.lastname: Chang
authors.forename: Filipp
authors.initials: F
authors.lastname: Savvulidi
authors.forename: Jana
authors.initials: J
authors.lastname: Michalová
authors.forename: Emanuel
authors.initials: E
authors.lastname: Nečas
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D047109:Fetal Development / Q000276:immunology*; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D008099:Liver / Q000196:embryology*; D038041:Lymphopoiesis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy
chemical_list: D004958:Estradiol