Permissive roles of cytokines Interleukin-7 and Flt3-ligand in mouse B cell lineage commitment
von Muenchow, Lilly Alberti-Servera, Llucia Klein, Fabian Capoferri, Giuseppina Finke, Daniela Ceredig, Rhodri Rolink, Antonius Tsapogas, Panagiotis
von Muenchow, Lilly
Alberti-Servera, Llucia
Klein, Fabian
Capoferri, Giuseppina
Finke, Daniela
Ceredig, Rhodri
Rolink, Antonius
Tsapogas, Panagiotis
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Publication Date
2016-11-04
Type
Article
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von Muenchow, Lilly, Alberti-Servera, Llucia, Klein, Fabian, Capoferri, Giuseppina, Finke, Daniela, Ceredig, Rhodri, Rolink, Antonius, 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, 113(50), E8122-E8130. doi: 10.1073/pnas.1613316113
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.
Publisher
National Academy of Sciences
Publisher DOI
10.1073/pnas.1613316113
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Attribution-NonCommercial-NoDerivs 3.0 Ireland