NDLI: The Interleukin 7 Receptor Is Required for T Cell Receptor γ Locus Accessibility to the V(D)j Recombinase

Content Provider	PubMed Central
Author	Schlissel, Mark S. Durum, Scott D. Muegge, Kathrin
Copyright Year	2000
Abstract	Defects in the interleukin (IL)-7 signal transduction pathway lead to severe immunodeficiency in humans and in mice. In IL-7 receptor–deficient (IL-7R−/−) mice, lymphoid precursors show a reduced survival rate and variable/diversity/joining region V(D)J recombination is variously affected in different loci, being arrested in the T cell receptor (TCR)-γ locus, aberrant in the immunoglobulin heavy chain (IgH) locus, and delayed in the TCR-β locus. Here, we analyze the recombination defect of the TCR-γ locus. Using ligation-mediated polymerase chain reaction, we sought intermediates of the recombination process. In the absence of the IL-7 signal, no initiation of recombination of the TCR-γ locus was observed, whereas recombination intermediates at the TCR-β locus could be detected. Thus, the failure to rearrange the TCR-γ locus is due to a failure to initiate cleavage rather than a failure to religate broken DNA ends. V(D)J recombination was previously thought to begin at the pro-T2 stage of T cell development after the arrest of IL-7R−/− thymocytes at the pro-T1 stage. However, here we show that both TCR-γ and -β recombination intermediates are readily detectable in normal T1 cells, but only TCR-β intermediates were detected in IL-7R−/− T1 cells, supporting a mechanistic role for IL-7 in TCR-γ locus rearrangement. Since reduced recombination activating gene (rag) expression has been reported in the absence of the IL-7 signal, we directly tested whether the TCR-γ locus is accessible to cleavage by recombinant Rag proteins in vitro. We found a reduction in chromatin accessibility for Rag-mediated cleavage in IL-7R−/− thymocytes compared with wild-type. Thus, IL-7 controls recombination at the TCR-γ locus by regulating locus accessibility.
Starting Page	1045
File Format	PDF
ISSN	15409538
e-ISSN	15409538
Journal	The Journal of Experimental Medicine
Issue Number	6
Volume Number	191
Language	English
Publisher	The Rockefeller University Press
Publisher Date	2000-03-20
Access Restriction	Open
Rights Holder	The Rockefeller University Press
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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Interallelic V(D)J trans-rearrangement within the beta T cell receptor gene is infrequent and occurs preferentially during attempted D beta to J beta joining

The Interleukin 7 Receptor Is Required for T Cell Receptor γ Locus Accessibility to the V(D)j Recombinase

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