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Permissive roles of cytokines interleukin-7 and Flt3 ligand in mouse B-cell lineage commitment

von Muenchow, Lilly and Alberti-Servera, Llucia and Klein, Fabian and Capoferri, Giuseppina and Finke, Daniela and Ceredig, Rhodri and Rolink, Antonius and Tsapogas, Panagiotis. (2016) Permissive roles of cytokines interleukin-7 and Flt3 ligand in mouse B-cell lineage commitment. Proceedings of the National Academy of Sciences of the United States of America, 113 (50). E8122-E8130.

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Official URL: http://edoc.unibas.ch/52922/

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Molekulare Medizin in der P├Ądiatrie (Finke)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Molekulare Medizin in der P├Ądiatrie (Finke)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Children's Hospital > Developmental Immunology (Finke)
UniBasel Contributors:Finke, Daniela
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
ISSN:0027-8424
e-ISSN:1091-6490
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:06 Oct 2017 09:21
Deposited On:06 Oct 2017 09:21

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