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PMID: 2495537 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Synthesis of germ-line gamma 1 immunoglobulin heavy-chain transcripts in resting B cells: induction by interleukin 4 and inhibition by interferon gamma.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 8 ·1989-04-00 ·Pages 2829-33

Berton MT, Uhr JW, Vitetta ES

Abstract

Interleukin 4 (IL-4) induces the expression of IgG1 and IgE in lipopolysaccharide-stimulated B cells. Previous studies have suggested that heavy-chain class switching may be regulated by increasing the accessibility of specific switch regions to switch recombinases. In this study, we have used an RNase protection assay to demonstrate that IL-4 induces expression of germ-line gamma 1 transcripts in B cells within 4 hr of culture; induction is dose-dependent and is inhibited by interferon gamma. IL-4 alone is capable of inducing the expression of germ-line gamma 1 transcripts in small, resting B cells, but lipopolysaccharide enhances expression. The germ-line transcripts are the same size (1.8 and 3.4 kilobases) as the secreted and membrane forms of the functional gamma 1 mRNAs and presumably result from the splicing of an upstream switch-region exon(s) to the gamma 1 constant-region exon(s). These data strongly support the "accessibility" model for the regulation of isotype switching and suggest that lymphokines such as IL-4 may direct specific switch events by transcriptional activation of the corresponding switch regions.

MeSH Terms
Animals B-Lymphocytes/physiology Blotting, Northern Gene Expression Regulation/drug effects Gene Rearrangement, B-Lymphocyte, Heavy Chain Immunoglobulin Heavy Chains/genetics Immunoglobulin gamma-Chains/genetics Interferon-gamma/pharmacology Interleukin-4 Interleukins/pharmacology Lipopolysaccharides/pharmacology Mice Mice, Inbred BALB C RNA, Messenger/genetics Recombination, Genetic Transcription, Genetic/drug effects
Chemicals
Immunoglobulin Heavy Chains Immunoglobulin gamma-Chains Interleukins Lipopolysaccharides RNA, Messenger Interleukin-4 Interferon-gamma
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Berton M T
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Uhr J W
Vitetta E S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.86.8.2829
Published
1989-04-00
Pages
2829-33
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC287012
Subset
IM
Grants
NIAID NIH HHS · AI07945 · United States
NIAID NIH HHS · AI11851 · United States
NIAID NIH HHS · AI12789 · United States
External Links
PubMed source DOI: 10.1073/pnas.86.8.2829 PMC Full Text View journal details
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