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PMID: 8195714 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Independent regulation of DNA recombination and immunoglobulin (Ig) secretion during isotype switching to IgG1 and IgE.

The Journal of experimental medicine ·Vol. 179 ·No. 6 ·1994-06-01 ·Pages 1877-83

Purkerson JM, Isakson PC

Abstract

Induction of switch recombination to the gamma 1 and epsilon immunoglobulin (Ig) heavy chain loci was examined in B cells preactivated with anti-Ig (B lymphoblasts). In B lymphoblasts cultured with interleukin 4 (IL-4), IL-5 induced the accumulation of S micro-S gamma 1 rearrangements, but not epsilon recombination. Thus, IL-5 facilitates switch recombination directed to the gamma 1 heavy chain locus by IL-4, but additional signals are required to drive rearrangements to epsilon. Lipopolysaccharide (LPS), in the presence of IL-4, induced the accumulation of both S micro-S gamma 1 and S micro-S epsilon rearrangements, and cells treated with LPS exhibited 40-50-fold more S micro-S gamma 1 rearrangements than cells cultured with IL-5. Induction of switch recombination was not always associated with secretion of the respective Ig isotype, since concentrations of IL-4 that were sufficient to direct switch recombination to gamma 1 and epsilon in blasts treated with LPS failed to elicit secretion of IgG1 and IgE. These results demonstrate differential requirements for switch recombination to the gamma 1 and epsilon loci, as well as independent regulation of Ig gene rearrangement and secretion of each isotype.

MeSH Terms
Animals B-Lymphocytes/drug effects,immunology Base Sequence Cells, Cultured DNA/isolation & purification,metabolism DNA Primers Female Gene Expression Regulation Genes, Immunoglobulin Genes, Switch Immunoglobulin E/biosynthesis,genetics Immunoglobulin G/biosynthesis,classification,genetics Immunoglobulin Isotypes/biosynthesis,genetics Interleukin-4/pharmacology Interleukin-5/pharmacology Kinetics Mice Mice, Inbred BALB C Molecular Sequence Data Polymerase Chain Reaction Recombination, Genetic Restriction Mapping Spleen/immunology
Chemicals
DNA Primers Immunoglobulin G Immunoglobulin Isotypes Interleukin-5 Interleukin-4 Immunoglobulin E DNA
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Purkerson J M
Searle Research and Development, Monsanto Company, St. Louis, Missouri 63198.
Isakson P C
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.179.6.1877
Published
1994-06-01
Pages
1877-83
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191522
Subset
IM
Grants
NIAID NIH HHS · AI-29976 · United States
External Links
PubMed source DOI: 10.1084/jem.179.6.1877 PMC Full Text View journal details
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