Document Detail


A T cell controlled molecular pathway regulating the IgH locus: CD40-mediated activation of the IgH 3' enhancer.
MedLine Citation:
PMID:  8978695     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Immunoglobulin heavy chain (IgH) class switch recombination and regulation of IgH expression levels are processes suggested to be controlled by the IgH 3' enhancer. Here we demonstrate that CD40 or IgM receptor stimulation of primary B cells results in transactivation of this enhancer. 4-Hydroxy-3-nitrophenylacetyl (NIP)-BSA induction of a K46 B cell line expressing a chimeric NIP-specific CD40 single chain receptor results in a ligand receptor-dependent response of a 3' enhancer ETS/AP-1 minimal promoter construct. Gel retardation analysis and genomic footprinting experiments reveal that CD40 or IgM induction recruits NFAB (nuclear factors of activated B cells) to the ETS/AP-1 motif. While IgM signalling recruits c-Fos, JunB and Elf-1 (NFAB-I), only JunB and Elf-1 were observed following CD40 signalling (NFAB-II). CD40 signalling, however, induces a Fos family-related partner for JunB, which may account for the transcriptional activity observed by NFAB-II in K46 cells. We propose a model whereby CD40 and IgM receptor-mediated signalling converge in the process of 3' enhancer activation in B lymphocytes. Our data provide a putative molecular explanation as to why CD40L-deficient mice, and possibly patients with hyper-IgM syndrome, are unable to undergo T cell-dependent class switch recombination but respond properly upon lipopolysaccharide-induced switch recombination.
Authors:
P A Grant; T Andersson; M F Neurath; V Arulampalam; A Bauch; R Müller; M Reth; S Pettersson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The EMBO journal     Volume:  15     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  1996 Dec 
Date Detail:
Created Date:  1997-01-27     Completed Date:  1997-01-27     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  6691-700     Citation Subset:  IM    
Affiliation:
Center For Biotechnology, Karolinska Institute, Novum, Huddinge, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD40 / biosynthesis,  immunology*
B-Lymphocytes / immunology*
Cell Line
DNA-Binding Proteins / metabolism
Enhancer Elements, Genetic*
Genes, Immunoglobulin*
Genes, Reporter
Globins / biosynthesis
Immunoglobulin Heavy Chains / biosynthesis*,  genetics*
Immunoglobulin M / biosynthesis,  genetics
Mice
Mice, Transgenic
Nuclear Proteins
Polymerase Chain Reaction
Proto-Oncogene Proteins c-fos / metabolism
Proto-Oncogene Proteins c-jun / metabolism
Recombinant Fusion Proteins / biosynthesis
Signal Transduction
T-Lymphocytes / immunology*
Transcription Factors / metabolism
Transcriptional Activation
Transfection
Chemical
Reg. No./Substance:
0/Antigens, CD40; 0/DNA-Binding Proteins; 0/ELF1 protein, human; 0/Elf1 protein, mouse; 0/Immunoglobulin Heavy Chains; 0/Immunoglobulin M; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/Recombinant Fusion Proteins; 0/Transcription Factors; 9004-22-2/Globins
Comments/Corrections

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