Source:http://linkedlifedata.com/resource/pubmed/id/15114665
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2004-4-28
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pubmed:abstractText |
Clast5/Stra13/DEC1 is a member of the helix-loop-helix family of transcriptional repressors. We have previously shown that Clast5 is rapidly down-regulated upon B cell activation and its overexpression inhibits cell cycle progression in B lymphoma cells. In the present study, we show that Clast5 expression is developmentally regulated during B cell differentiation, being expressed at the progenitor B cells, down-regulated at the precursor B cells, elevated in immature and mature resting B lymphocytes, and down-regulated again in germinal center B cells. To investigate the function of Clast5 in regulating lymphocyte development, we have generated transgenic mice expressing Clast5 in B- and T-lineage cells (Clast5-Tg). Clast5-Tg mice grew and bred normally but their spleen and thymus cellularity was reduced compared with control littermates. The development of B cells in the bone marrow and T cells in the thymus was impaired, with the expansion of progenitor B and T cells most strongly affected. The frequency of IL-7-responsive cells in the bone marrow of Clast5-Tg mice was reduced by >80% and their proliferative response to IL-7 was also compromised. Mature B cells from Clast5-Tg mice were hyporesponsive to antigen receptor cross-linking and exhibited mild reduction in the proliferative response to CD40 ligation or lipopolysaccharide stimulation. Moreover, the development of germinal center B cells and antibody production against a T-dependent antigen were reduced in Clast5-Tg mice. These results reveal a critical role for Clast5/Stra13/DEC1 in negatively regulating lymphocyte development and function in vivo.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0014-2980
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pubmed:author |
pubmed-author:HatanoMasahikoM,
pubmed-author:KawamuraKiyokoK,
pubmed-author:O-WangJiyangJ,
pubmed-author:OhkuboYusukeY,
pubmed-author:OkadaSeijiS,
pubmed-author:SaishoHiromitsuH,
pubmed-author:SakamotoAkemiA,
pubmed-author:SeimiyaMikaM,
pubmed-author:TagawaMasatoshiM,
pubmed-author:TokuhisaTakeshiT,
pubmed-author:WadaAkihikoA,
pubmed-author:WatanabeTakeshiT
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pubmed:issnType |
Print
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1322-32
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15114665-Animals,
pubmed-meshheading:15114665-Autoimmune Diseases,
pubmed-meshheading:15114665-B-Lymphocytes,
pubmed-meshheading:15114665-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:15114665-Cell Differentiation,
pubmed-meshheading:15114665-Disease Models, Animal,
pubmed-meshheading:15114665-Homeodomain Proteins,
pubmed-meshheading:15114665-Interleukin-7,
pubmed-meshheading:15114665-Mice,
pubmed-meshheading:15114665-Mice, Transgenic,
pubmed-meshheading:15114665-T-Lymphocytes,
pubmed-meshheading:15114665-Thymus Gland
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pubmed:year |
2004
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pubmed:articleTitle |
Impaired lymphocyte development and function in Clast5/Stra13/DEC1-transgenic mice.
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pubmed:affiliation |
Division of Pathology, Chiba Cancer Center Research Institute, Chiba, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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