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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
1997-6-2
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pubmed:abstractText |
Transcription of unrearranged (germline) Ig heavy chain C region (C(H)) genes is required before Ab class switch recombination. Although the cytokine IL-4 is well known to induce transcription of unrearranged C epsilon and C gamma1 genes, it has been shown recently that CD40 signaling also induces these transcripts in mouse B cells. We report in this study that treatment of mouse M12.4.1 B lymphoma cells with soluble CD40 ligand (CD40L)-CD8alpha fusion protein modestly induces the promoter for germline epsilon transcripts, and that this induction synergizes with IL-4. CD40L induces binding of nuclear factor (NF)-kappaB/Rel proteins to two tandem kappaB sites located immediately 3' to the IL-4-responsive region of the mouse germline epsilon promoter. The epsilon-124/-56 promoter segment containing the IL-4 response region and the two kappaB sites is sufficient to transfer CD40L and IL-4 inducibility to a minimal c-fos promoter when transiently transfected into M12.4.1 cells. Mutation of the two kappaB sites eliminates induction by CD40L or by IL-4, and treatment of M12.4.1 cells with inhibitors of NF-kappaB activation prevents induction of endogenous germline epsilon transcripts in M12.4.1 cells. In addition to the NF-kappaB/Rel complexes induced by CD40L, two nuclear complexes, each which contain both STAT6 and NF-kappaB/Rel proteins, are induced in splenic B cells by a combination of CD40L and IL-4, and bind to the CD40L/IL-4-responsive region of the germline epsilon promoter. The presence of these complexes may explain the synergistic induction of transcription by CD40L and IL-4 mediated through this promoter segment.
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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/Antigens, CD40,
http://linkedlifedata.com/resource/pubmed/chemical/CD40 Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin E,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/STAT6 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
158
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4769-79
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9144491-Animals,
pubmed-meshheading:9144491-Antigens, CD40,
pubmed-meshheading:9144491-B-Lymphocytes,
pubmed-meshheading:9144491-Base Sequence,
pubmed-meshheading:9144491-Binding Sites,
pubmed-meshheading:9144491-CD40 Ligand,
pubmed-meshheading:9144491-DNA-Binding Proteins,
pubmed-meshheading:9144491-Genes, Immunoglobulin,
pubmed-meshheading:9144491-Immunoglobulin E,
pubmed-meshheading:9144491-Interleukin-4,
pubmed-meshheading:9144491-Membrane Glycoproteins,
pubmed-meshheading:9144491-Mice,
pubmed-meshheading:9144491-Molecular Sequence Data,
pubmed-meshheading:9144491-NF-kappa B,
pubmed-meshheading:9144491-Promoter Regions, Genetic,
pubmed-meshheading:9144491-STAT6 Transcription Factor,
pubmed-meshheading:9144491-Signal Transduction,
pubmed-meshheading:9144491-Trans-Activators,
pubmed-meshheading:9144491-Transcription, Genetic
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pubmed:year |
1997
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pubmed:articleTitle |
CD40 cross-linking induces Ig epsilon germline transcripts in B cells via activation of NF-kappaB: synergy with IL-4 induction.
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pubmed:affiliation |
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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