Source:http://linkedlifedata.com/resource/pubmed/id/16301649
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2005-11-22
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pubmed:abstractText |
During the adaptive phase of an immune response, naive B cells receive multiple signals to become activated. Among them are the engagement of the B cell Ag receptor and stimulation by cytokines. Specifically for an anti-microbial response, the recognition of viral or bacterial Ags by the BCR and the stimulation of IFN-gamma result in the predominant production of IgG2a. The T-bet protein has been shown to be required for class switching to IgG2a. In this report we further investigated the regulation of T-bet gene expression during the early stage of B cell activation. We show that there is a striking synergistic activation of T-bet in primary B cells when both the BCR and IFN-gamma signaling pathways are activated. The synergistic activation of T-bet correlates with a 100% increase in the number of B cells that produce IgG2a. This transcription synergy on T-bet is transient in the first 24 h of B cell activation. Furthermore, we demonstrate that the synergistic activation of T-bet is dependent on Stat1 and that Stat1 is required for the IgG2a germline transcription and the production of IgG2a in response to the simultaneous signaling of BCR and IFN-gamma. Finally, we show that Stat1 directly regulates the expression of T-bet by binding to the T-bet promoter. These results reveal the mechanism of regulation of T-bet expression and uncover a novel physiological function of Stat1 for B cell activation.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/T-Box Domain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/T-box transcription factor TBX21,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
175
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7419-24
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16301649-Animals,
pubmed-meshheading:16301649-B-Lymphocytes,
pubmed-meshheading:16301649-Blotting, Western,
pubmed-meshheading:16301649-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:16301649-Flow Cytometry,
pubmed-meshheading:16301649-Gene Expression,
pubmed-meshheading:16301649-Gene Expression Regulation,
pubmed-meshheading:16301649-Immunoglobulin Class Switching,
pubmed-meshheading:16301649-Immunoglobulin G,
pubmed-meshheading:16301649-Interferon-gamma,
pubmed-meshheading:16301649-Lymphocyte Activation,
pubmed-meshheading:16301649-Mice,
pubmed-meshheading:16301649-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16301649-STAT1 Transcription Factor,
pubmed-meshheading:16301649-T-Box Domain Proteins,
pubmed-meshheading:16301649-Transcription Factors
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pubmed:year |
2005
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pubmed:articleTitle |
Stat1-dependent synergistic activation of T-bet for IgG2a production during early stage of B cell activation.
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pubmed:affiliation |
Department of Pathology and Molecular Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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