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PMID: 10770800 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Immunoglobulin beta signaling regulates locus accessibility for ordered immunoglobulin gene rearrangements.

The Journal of experimental medicine ·Vol. 191 ·No. 8 ·2000-04-17 ·Pages 1333-40

Maki K, Nagata K, Kitamura F, Takemori T, Karasuyama H

Abstract

The antigen receptor gene rearrangement at a given locus is tightly regulated with respect to cell lineage and developmental stage by an ill-defined mechanism. To study the possible role of precursor B cell antigen receptor (pre-BCR) signaling in the regulation of the ordered immunoglobulin (Ig) gene rearrangement during B cell differentiation, a newly developed system using mu heavy (H) chain membrane exon (microm)-deficient mice was employed. In this system, the antibody-mediated cross-linking of Igbeta on developmentally arrested progenitor B (pro-B) cells mimicked pre-BCR signaling to induce early B cell differentiation in vivo. Analyses with ligation-mediated polymerase chain reaction revealed that the Igbeta cross-linking induced the redirection of Ig gene rearrangements, namely, the suppression of ongoing rearrangements at the H chain locus and the activation of rearrangements at the light (L) chain locus. Upon the cross-linking, the kappaL chain germline transcription was found to be upregulated whereas the V(H) germline transcription was promptly downregulated. Notably, this alteration of the accessibility at the H and L chain loci was detected even before the induction of cellular differentiation became detectable by the change of surface phenotype. Thus, the pre-BCR signaling through Igbeta appears to regulate the ordered Ig gene rearrangement by altering the Ig locus accessibility.

MeSH Terms
Animals Antibodies, Anti-Idiotypic/pharmacology Antibodies, Monoclonal/pharmacology B-Lymphocytes/cytology,immunology Base Sequence Cell Differentiation Cross-Linking Reagents/pharmacology DNA Primers/genetics Gene Rearrangement, B-Lymphocyte, Heavy Chain Hematopoiesis Hematopoietic Stem Cells/cytology,immunology Mice Mice, Knockout Receptors, Antigen, B-Cell/genetics Signal Transduction
Chemicals
Antibodies, Anti-Idiotypic Antibodies, Monoclonal Cross-Linking Reagents DNA Primers Receptors, Antigen, B-Cell
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Maki K
Department of Immunology, Tokyo Metropolitan Organization for Medical Research, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan.
Nagata K
Kitamura F
Takemori T
Karasuyama H
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.191.8.1333
Published
2000-04-17
Pages
1333-40
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193127
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.191.8.1333 PMC Full Text View journal details
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