| STAT6 is required for IL-4-induced germline Ig gene transcription and switch recombination. | |
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MedLine Citation:
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PMID: 9647237 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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L A Linehan; W D Warren; P A Thompson; M J Grusby; M T Berton |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 161 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 1998 Jul |
Date Detail:
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Created Date: 1998-07-09 Completed Date: 1998-07-09 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 302-10 Citation Subset: AIM; IM |
Affiliation:
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Department of Microbiology, University of Texas Health Science Center, San Antonio 78284, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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AI40171/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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