Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1997-6-2
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
158
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4769-79
pubmed:dateRevised
2008-11-21
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
pubmed:year
1997
pubmed:articleTitle
CD40 cross-linking induces Ig epsilon germline transcripts in B cells via activation of NF-kappaB: synergy with IL-4 induction.
pubmed:affiliation
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't