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PMID: 10770803 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Evidence for class-specific factors in immunoglobulin isotype switching.

The Journal of experimental medicine ·Vol. 191 ·No. 8 ·2000-04-17 ·Pages 1365-80

Shanmugam A, Shi MJ, Yauch L, Stavnezer J, Kenter AL

Abstract

Immunoglobulin class switch recombination (SR) occurs by a B cell-specific, intrachromosomal deletional process between switch regions. We have developed a plasmid-based transient transfection assay for SR to test for the presence of transacting switch activities. The plasmids are novel in that they lack a eukaryotic origin of DNA replication. The recombination activity of these switch substrates is restricted to a subset of B cell lines that support isotype switching on their endogenous loci and to mitogen-activated normal splenic B cells. The factors required for extrachromosomal plasmid recombination are constitutively expressed in proliferating splenic B cells and in B cell lines capable of inducibly undergoing immunoglobulin SR on their chromosomal genes. These studies suggest that mitogens that induce switching on the chromosome induce accessibility rather than switch recombinase activity. Finally, we provide evidence for two distinct switching activities which independently mediate mu-->alpha and mu-->gamma3 SR.

MeSH Terms
Animals B-Lymphocytes/immunology Base Sequence Cell Line DNA/genetics DNA Primers/genetics Escherichia coli/genetics Immunoglobulin Isotypes/classification,genetics Immunoglobulin Switch Region Mice Mice, Inbred BALB C Mice, Nude Molecular Sequence Data Plasmids/genetics Polymerase Chain Reaction Transcription, Genetic Transfection Transformation, Genetic
Chemicals
DNA Primers Immunoglobulin Isotypes DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shanmugam A
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA.
Shi M J
Yauch L
Stavnezer J
Kenter A L
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.191.8.1365
Published
2000-04-17
Pages
1365-80
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193137
Subset
IM
Grants
NIAID NIH HHS · R21 AI106328 · United States
NIGMS NIH HHS · GM57078 · United States
NIAID NIH HHS · AI23283 · United States
External Links
PubMed source DOI: 10.1084/jem.191.8.1365 PMC Full Text View journal details
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