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rdf:type |
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lifeskim:mentions |
umls-concept:C0038952,
umls-concept:C0079411,
umls-concept:C0249989,
umls-concept:C0441889,
umls-concept:C0449864,
umls-concept:C0870134,
umls-concept:C1514873,
umls-concept:C1518071,
umls-concept:C1522457,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1709634
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pubmed:issue |
2
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pubmed:dateCreated |
2011-1-26
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pubmed:abstractText |
The generation of B-cell precursors (BCP) from lymphohematopoietic progenitors (LHP) in bone marrow is dependent on signals provided by the receptor tyrosine kinase Flt3 and its ligand, Flt3-ligand (FL). Mice deficient in FL exhibit striking reductions in LHP and BCP. Currently, the mechanism by which Flt3 regulates lymphoid lineage/B-cell development is unknown. Here, we show that haploinsufficiency of FL (FL(+/) (-) ) reduced the numbers of LHP, common lymphoid progenitors, and pro-B cells, suggesting that FL levels set a threshold for B lymphopoiesis. Limiting dilution analysis confirmed reduced BCP frequency in FL(+/) (-) mice. Real-time PCR of LHP from FL(+/) (-) animals showed increased transcripts of the B lineage inhibitor id1. However, targeted deletion of id1 did not restore the lymphoid/B lineage deficiencies in FL(-/-) mice, supporting Id1-independent mechanisms. BrdU incorporation studies established that FL is not essential for the proliferation of Flt3(+) multipotential progenitors. Analysis of FL(-/-) progenitors expressing low levels of Flt3 revealed decreased levels of the pro-survival factor Mcl1. Consequently, the Flt3(+) LHP progeny of Flt3(low) LSK(+) cells exhibited increased Annexin V staining. Together, these data suggest that Flt3 signaling initiates a cascade of events in Flt3(low) precursors that promote the survival of LHP from which BCP are derived.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Flt3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Idb1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Differentiation...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RAG-1 protein,
http://linkedlifedata.com/resource/pubmed/chemical/flt3 ligand protein,
http://linkedlifedata.com/resource/pubmed/chemical/fms-Like Tyrosine Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/myeloid cell leukemia sequence 1...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1521-4141
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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pubmed:issnType |
Electronic
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
324-34
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pubmed:dateRevised |
2011-5-5
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pubmed:meshHeading |
pubmed-meshheading:21268003-Animals,
pubmed-meshheading:21268003-Apoptosis,
pubmed-meshheading:21268003-Bone Marrow Cells,
pubmed-meshheading:21268003-Cell Count,
pubmed-meshheading:21268003-Cell Proliferation,
pubmed-meshheading:21268003-Cell Survival,
pubmed-meshheading:21268003-Gene Expression,
pubmed-meshheading:21268003-Haploinsufficiency,
pubmed-meshheading:21268003-Heterozygote,
pubmed-meshheading:21268003-Homeodomain Proteins,
pubmed-meshheading:21268003-Inhibitor of Differentiation Protein 1,
pubmed-meshheading:21268003-Lymphoid Progenitor Cells,
pubmed-meshheading:21268003-Lymphopoiesis,
pubmed-meshheading:21268003-Membrane Proteins,
pubmed-meshheading:21268003-Mice,
pubmed-meshheading:21268003-Mice, Inbred C57BL,
pubmed-meshheading:21268003-Mice, Knockout,
pubmed-meshheading:21268003-Mice, Transgenic,
pubmed-meshheading:21268003-Multipotent Stem Cells,
pubmed-meshheading:21268003-Precursor Cells, B-Lymphoid,
pubmed-meshheading:21268003-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:21268003-Signal Transduction,
pubmed-meshheading:21268003-fms-Like Tyrosine Kinase 3
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pubmed:year |
2011
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pubmed:articleTitle |
Threshold levels of Flt3-ligand are required for the generation and survival of lymphoid progenitors and B-cell precursors.
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pubmed:affiliation |
Department of Immunology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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