title: Embryonic day 9 yolk sac and intra-embryonic hemogenic endothelium independently generate a B-1 and marginal zone progenitor lacking B-2 potential.
abstract: The majority of B lymphocytes in the adult mouse are generated in the bone marrow from hematopoietic stem cells (HSCs) that first appear in the aorta-gonado-mesonephros region of the fetus on embryonic day (E) 10.5-11. Comparatively less is known about B-cell development during embryogenesis. For example, which specific embryonic tissues participate in B lymphopoiesis and whether hematopoietic differentiation is skewed toward specific B-cell subsets in the embryo are unanswered questions, because the systemic circulation is initiated early during embryogenesis, resulting in an admixture of cells potentially originating from multiple sites. We demonstrate, using Ncx1(-/-) mice that lack systemic blood circulation, that the E9 yolk sac (YS) and the intra-embryonic para-aortic splanchnopleura (P-Sp) tissues independently give rise to AA4.1(+)CD19(+)B220(lo-neg) B progenitor cells that preferentially differentiate into innate type B-1 and marginal zone (MZ) B cells but not into B-2 cells upon transplantation. We have further demonstrated that these B-1 progenitor cells arise directly from YS and P-Sp hemogenic endothelium. These results document the initial wave of innate B lymphopoietic progenitor cells available for seeding the fetal liver at E11. The results of these studies expand our knowledge of hemogenic endothelial sites specifying distinct B-1 and MZ cell fates apart from B-2 cells and independent of an HSC origin during development.
authors.affiliation: Department of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Momoko
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Encarnacion
authors.initials: E
authors.lastname: Montecino-Rodriguez
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ferkowicz
authors.forename: Prashanth
authors.initials: P
authors.lastname: Porayette
authors.forename: W Christopher
authors.initials: WC
authors.lastname: Shelley
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dorshkind
authors.forename: Mervin C
authors.initials: MC
authors.lastname: Yoder
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D019070:Cell Lineage; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D055018:Hemangioblasts / Q000166:cytology* / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006413:Hematopoietic System / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D038041:Lymphopoiesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D011247:Pregnancy; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D015017:Yolk Sac / Q000166:cytology* / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; C499849:NCX1 protein, mouse; D019831:Sodium-Calcium Exchanger; D017493:Leukocyte Common Antigens