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PMID: 3139821 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Feedback inhibition of immunoglobulin gene rearrangement by membrane mu, but not by secreted mu heavy chains.

The Journal of experimental medicine ·Vol. 168 ·No. 4 ·1988-10-01 ·Pages 1363-81

Manz J, Denis K, Witte O, Brinster R, Storb U

Abstract

Previous work (6-10) has shown that allelic exclusion of Ig gene expression is controlled by functionally rearranged mu and kappa genes. This report deals with the comparison of membrane mu (micron) and secreted mu (microsecond) in promoting such feedback inhibition. Splenic B cell hybridomas were analyzed from transgenic mice harboring a rearranged kappa gene alone or in combination with either an intact rearranged mu gene or a truncated version of the mu gene. The intact mu gene is capable of producing both membrane and secreted forms of the protein, while the truncated version can only encode the secreted form. The role of the microsecond was also tested in pre-B cell lines. Analysis of the extent of endogenous Ig gene rearrangement revealed that (a) the production of micron together with kappa can terminate Ig gene rearrangement; (b) microsecond with kappa does not have this feedback effect; (c) microsecond may interfere with the effect of micron and kappa; and (d) the feedback shown here probably represents a complete shutoff of the specific recombinase by micron + kappa; the data do not address the question of mu alone affecting the accessibility of H genes for rearrangement.

MeSH Terms
Animals B-Lymphocytes/immunology Blotting, Southern Cell Line DNA/analysis DNA Probes Gene Rearrangement, B-Lymphocyte Gene Rearrangement, B-Lymphocyte, Heavy Chain Gene Rearrangement, B-Lymphocyte, Light Chain Hybridomas Immunoglobulin Heavy Chains/genetics Immunoglobulin kappa-Chains/genetics Immunoglobulin mu-Chains/genetics Mice Mice, Transgenic Nucleic Acid Hybridization
Chemicals
DNA Probes Immunoglobulin Heavy Chains Immunoglobulin kappa-Chains Immunoglobulin mu-Chains DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Manz J
Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637.
Denis K
Witte O
Brinster R
Storb U
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49 references, click to expand
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.168.4.1363
Published
1988-10-01
Pages
1363-81
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2189090
Subset
IM
Grants
NIAID NIH HHS · AI 24780 · United States
NICHD NIH HHS · HD 17321 · United States
NICHD NIH HHS · HD 23089 · United States
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1084/jem.168.4.1363 PMC Full Text View journal details
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