Document Detail


STAT6 is required for IL-4-induced germline Ig gene transcription and switch recombination.
MedLine Citation:
PMID:  9647237     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transcription of the germline C gamma1 and C epsilon Ig genes is believed to be a necessary prerequisite for isotype switching to IgG1 and IgE, respectively. IL-4 stimulation and ligation of CD40 can each independently induce low level germline gamma1 and epsilon transcription in murine B cells. Together these signals act synergistically to promote high level germline transcription and are normally required for T-dependent isotype switching to IgG1 and IgE. The STAT6 transcription factor has been suggested to play a critical role in IL-4-induced activation of germline C gamma1 and C epsilon genes. To directly assess the role of STAT6 in IL-4R- and CD40-mediated germline transcription and switching, we have analyzed these events in splenic B cells from STAT6-deficient mice. Our results demonstrate that IL-4 does not induce detectable levels of germline gamma1 or epsilon transcripts in STAT6-deficient B cells. Germline transcript expression induced by CD40 stimulation alone is unaffected, but synergism between CD40- and IL-4R-mediated signals is completely ablated. Switch recombination to S gamma1, as measured by digestion-circularization PCR, is dramatically reduced in STAT6-deficient B cells stimulated with CD40 ligand plus IL-4. Similarly, germline gamma1 transcript expression and switch recombination to S gamma1 are also impaired in STAT6-deficient B cells stimulated with IL-4, IL-5, and anti-IgD Abs conjugated to dextran, a model for T-independent type II responses. These results directly demonstrate a critical role for STAT6 in the IL-4-mediated activation of germline Ig gene transcription and switch recombination in nontransformed B cells.
Authors:
L A Linehan; W D Warren; P A Thompson; M J Grusby; M T Berton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  161     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1998 Jul 
Date Detail:
Created Date:  1998-07-09     Completed Date:  1998-07-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  302-10     Citation Subset:  AIM; IM    
Affiliation:
Department of Microbiology, University of Texas Health Science Center, San Antonio 78284, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD40 / physiology
Antigens, T-Independent / genetics
B-Lymphocytes / immunology
CD40 Ligand
Cells, Cultured
DNA-Binding Proteins / metabolism
Gene Expression Regulation / immunology
Genes, Immunoglobulin*
Immunoglobulin Class Switching / genetics,  immunology*
Immunoglobulin G / genetics
Immunoglobulin epsilon-Chains / genetics
Immunoglobulin gamma-Chains / biosynthesis,  genetics
Interleukin-4 / genetics,  metabolism,  physiology*
Ligands
Lymphocyte Activation / genetics
Membrane Glycoproteins / physiology
Mice
Mice, Inbred BALB C
Mice, Knockout
STAT6 Transcription Factor
T-Lymphocytes / immunology
Trans-Activators / genetics,  physiology*
Transcription, Genetic / immunology*
Grant Support
ID/Acronym/Agency:
AI40171/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD40; 0/Antigens, T-Independent; 0/DNA-Binding Proteins; 0/Immunoglobulin G; 0/Immunoglobulin epsilon-Chains; 0/Immunoglobulin gamma-Chains; 0/Ligands; 0/Membrane Glycoproteins; 0/STAT6 Transcription Factor; 0/Stat6 protein, mouse; 0/Trans-Activators; 147205-72-9/CD40 Ligand; 207137-56-2/Interleukin-4

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