title: Permissive roles of cytokines interleukin-7 and Flt3 ligand in mouse B-cell lineage commitment.
abstract: Hematopoietic cells are continuously generated throughout life from hematopoietic stem cells, thus making hematopoiesis a favorable system to study developmental cell lineage commitment. The main factors incorporating environmental signals to developing hematopoietic cells are cytokines, which regulate commitment of hematopoietic progenitors to the different blood lineages by acting either in an instructive or a permissive manner. Fms-like tyrosine kinase-3 (Flt3) ligand (FL) and Interleukin-7 (IL-7) are cytokines pivotal for B-cell development, as manifested by the severely compromised B-cell development in their absence. However, their precise role in regulating B-cell commitment has been the subject of debate. In the present study we assessed the rescue of B-cell commitment in mice lacking IL-7 but simultaneously overexpressing FL. Results obtained demonstrate that FL overexpression in IL-7-deficient mice rescues B-cell commitment, resulting in significant Ebf1 and Pax5 expression in Ly6D+CD135+CD127+CD19-precursors and subsequent generation of normal numbers of CD19+B-cell progenitors, therefore indicating that IL-7 can be dispensable for commitment to the B-cell lineage. Further analysis of Ly6D+CD135+CD127+CD19-progenitors in IL-7- or FL-deficient mice overexpressing Bcl2, as well as in IL-7 transgenic mice suggests that both FL and IL-7 regulate B-cell commitment in a permissive manner: FL by inducing proliferation of Ly6D+CD135+CD127+CD19-progenitors and IL-7 by providing survival signals to these progenitors.
authors.affiliation: Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
authors.forename: Lilly
authors.initials: L
authors.lastname: von Muenchow
authors.affiliation: Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
authors.forename: Llucia
authors.initials: L
authors.lastname: Alberti-Servera
authors.affiliation: Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Klein
authors.affiliation: Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Capoferri
authors.affiliation: Research Department, University Children's Hospital Basel, 4056 Basel, Switzerland.|Developmental Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Finke
authors.affiliation: Discipline of Physiology, National University of Ireland, H91 DK59 Galway, Ireland.
authors.forename: Rhodri
authors.initials: R
authors.lastname: Ceredig
authors.affiliation: Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
authors.forename: Antonius
authors.initials: A
authors.lastname: Rolink
authors.affiliation: Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland; panagiotis.tsapogas@unibas.ch.
authors.forename: Panagiotis
authors.identifier: 0000-0002-9450-2604
authors.initials: P
authors.lastname: Tsapogas
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D019070:Cell Lineage / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006410:Hematopoiesis / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015851:Interleukin-7 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic
chemical_list: D018941:Antigens, CD19; D000950:Antigens, Ly; C000604812:CD19 antigen, mouse; D058851:GPI-Linked Proteins; D015851:Interleukin-7; C035271:Ly6d protein, mouse; D008565:Membrane Proteins; C084881:flt3 ligand protein
keywords: commitment; cytokines; hematopoiesis; immunology