title: Fetal Hematopoietic Stem Cell Transplantation Fails to Fully Regenerate the B-Lymphocyte Compartment.
abstract: B cells are key components of cellular and humoral immunity and, like all lymphocytes, are thought to originate and renew from hematopoietic stem cells (HSCs). However, our recent single-HSC transfer studies demonstrate that adult bone marrow HSCs do not regenerate B-1a, a subset of tissue B cells required for protection against pneumonia, influenza, and other infections. Since B-1a are regenerated by transfers of fetal liver, the question arises as to whether B-1a derive from fetal, but not adult, HSCs. Here we show that, similar to adult HSCs, fetal HSCs selectively fail to regenerate B-1a. We also show that, in humanized mice, human fetal liver regenerates tissue B cells that are phenotypically similar to murine B-1a, raising the question of whether human HSC transplantation, the mainstay of such models, is sufficient to regenerate human B-1a. Thus, our studies overtly challenge the current paradigm that HSCs give rise to all components of the immune system.
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: eliverg@stanford.edu.
authors.forename: Eliver Eid Bou
authors.initials: EE
authors.lastname: Ghosn
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Waters
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Phillips
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamamoto
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Long
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Gerstein
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Stoddart
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Leonore A
authors.initials: LA
authors.lastname: Herzenberg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D053686:Fetal Stem Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D016332:Fetal Tissue Transplantation / Q000379:methods*; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D008164:Luminescent Proteins