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Processing of Switch Transcripts Is Required for Targeting of Antibody Class Switch Recombination

Antibody class switching is mediated by somatic recombination between switch regions of the immunoglobulin heavy chain gene locus. Targeting of recombination to particular switch regions is strictly regulated by cytokines through the induction of switch transcripts starting 5′ of the repetitive swit...

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Detalles Bibliográficos
Autores principales: Hein, Katharina, Lorenz, Matthias G.O., Siebenkotten, Gregor, Petry, Katja, Christine, Rainer, Radbruch, Andreas
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212419/
https://www.ncbi.nlm.nih.gov/pubmed/9858523
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author Hein, Katharina
Lorenz, Matthias G.O.
Siebenkotten, Gregor
Petry, Katja
Christine, Rainer
Radbruch, Andreas
author_facet Hein, Katharina
Lorenz, Matthias G.O.
Siebenkotten, Gregor
Petry, Katja
Christine, Rainer
Radbruch, Andreas
author_sort Hein, Katharina
collection PubMed
description Antibody class switching is mediated by somatic recombination between switch regions of the immunoglobulin heavy chain gene locus. Targeting of recombination to particular switch regions is strictly regulated by cytokines through the induction of switch transcripts starting 5′ of the repetitive switch regions. However, switch transcription as such is not sufficient to target switch recombination. This has been shown in mutant mice, in which the I-exon and its promoter upstream of the switch region were replaced with heterologous promoters. Here we show that, in the murine germline targeted replacement of the endogenous γ1 promoter, I-exon, and I-exon splice donor site by heterologous promoter and splice donor sites directs switch recombination in activated B lymphocytes constitutively to the γ1 switch region. In contrast, switch recombination to IgG1 is inhibited in mutant mice, in which the replacement does not include the heterologous splice donor site. Our data unequivocally demonstrate that targeting of switch recombination to IgG1 in vivo requires processing of the Iγ1 switch transcripts. Either the processing machinery or the processed transcripts are involved in class switch recombination.
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spelling pubmed-22124192008-04-16 Processing of Switch Transcripts Is Required for Targeting of Antibody Class Switch Recombination Hein, Katharina Lorenz, Matthias G.O. Siebenkotten, Gregor Petry, Katja Christine, Rainer Radbruch, Andreas J Exp Med Brief Definitive Reports Antibody class switching is mediated by somatic recombination between switch regions of the immunoglobulin heavy chain gene locus. Targeting of recombination to particular switch regions is strictly regulated by cytokines through the induction of switch transcripts starting 5′ of the repetitive switch regions. However, switch transcription as such is not sufficient to target switch recombination. This has been shown in mutant mice, in which the I-exon and its promoter upstream of the switch region were replaced with heterologous promoters. Here we show that, in the murine germline targeted replacement of the endogenous γ1 promoter, I-exon, and I-exon splice donor site by heterologous promoter and splice donor sites directs switch recombination in activated B lymphocytes constitutively to the γ1 switch region. In contrast, switch recombination to IgG1 is inhibited in mutant mice, in which the replacement does not include the heterologous splice donor site. Our data unequivocally demonstrate that targeting of switch recombination to IgG1 in vivo requires processing of the Iγ1 switch transcripts. Either the processing machinery or the processed transcripts are involved in class switch recombination. The Rockefeller University Press 1998-12-21 /pmc/articles/PMC2212419/ /pubmed/9858523 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Reports
Hein, Katharina
Lorenz, Matthias G.O.
Siebenkotten, Gregor
Petry, Katja
Christine, Rainer
Radbruch, Andreas
Processing of Switch Transcripts Is Required for Targeting of Antibody Class Switch Recombination
title Processing of Switch Transcripts Is Required for Targeting of Antibody Class Switch Recombination
title_full Processing of Switch Transcripts Is Required for Targeting of Antibody Class Switch Recombination
title_fullStr Processing of Switch Transcripts Is Required for Targeting of Antibody Class Switch Recombination
title_full_unstemmed Processing of Switch Transcripts Is Required for Targeting of Antibody Class Switch Recombination
title_short Processing of Switch Transcripts Is Required for Targeting of Antibody Class Switch Recombination
title_sort processing of switch transcripts is required for targeting of antibody class switch recombination
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212419/
https://www.ncbi.nlm.nih.gov/pubmed/9858523
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