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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21 December 1998
Brief Definitive Report|
December 21 1998
Processing of Switch Transcripts Is Required for Targeting of Antibody Class Switch Recombination
Katharina Hein,
Katharina Hein
From the *Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany; ‡the National Institutes of Health, National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, Maryland 20892; and §AMAXA GmbH, c/o Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany
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Matthias G.O. Lorenz,
Matthias G.O. Lorenz
From the *Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany; ‡the National Institutes of Health, National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, Maryland 20892; and §AMAXA GmbH, c/o Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany
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Gregor Siebenkotten,
Gregor Siebenkotten
From the *Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany; ‡the National Institutes of Health, National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, Maryland 20892; and §AMAXA GmbH, c/o Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany
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Katja Petry,
Katja Petry
From the *Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany; ‡the National Institutes of Health, National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, Maryland 20892; and §AMAXA GmbH, c/o Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany
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Rainer Christine,
Rainer Christine
From the *Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany; ‡the National Institutes of Health, National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, Maryland 20892; and §AMAXA GmbH, c/o Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany
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Andreas Radbruch
Andreas Radbruch
From the *Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany; ‡the National Institutes of Health, National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, Maryland 20892; and §AMAXA GmbH, c/o Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany
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Katharina Hein
From the *Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany; ‡the National Institutes of Health, National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, Maryland 20892; and §AMAXA GmbH, c/o Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany
Matthias G.O. Lorenz
From the *Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany; ‡the National Institutes of Health, National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, Maryland 20892; and §AMAXA GmbH, c/o Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany
Gregor Siebenkotten
From the *Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany; ‡the National Institutes of Health, National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, Maryland 20892; and §AMAXA GmbH, c/o Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany
Katja Petry
From the *Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany; ‡the National Institutes of Health, National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, Maryland 20892; and §AMAXA GmbH, c/o Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany
Rainer Christine
From the *Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany; ‡the National Institutes of Health, National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, Maryland 20892; and §AMAXA GmbH, c/o Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany
Andreas Radbruch
From the *Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany; ‡the National Institutes of Health, National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, Maryland 20892; and §AMAXA GmbH, c/o Deutsches Rheuma-Forschungszentrum Berlin, 10115 Berlin, Germany
Address correspondence to Andreas Radbruch, Deutsches Rheuma-Forschungszentrum Berlin, Hannoversche Strasse 27, 10115 Berlin, Germany. Phone: 0049-30-2851-8980; Fax: 0049-30-2851-8910; E-mail: radbruch @drfz.de
Received:
August 24 1998
Revision Received:
October 05 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (12): 2369–2374.
Article history
Received:
August 24 1998
Revision Received:
October 05 1998
Citation
Katharina Hein, Matthias G.O. Lorenz, Gregor Siebenkotten, Katja Petry, Rainer Christine, Andreas Radbruch; Processing of Switch Transcripts Is Required for Targeting of Antibody Class Switch Recombination . J Exp Med 21 December 1998; 188 (12): 2369–2374. doi: https://doi.org/10.1084/jem.188.12.2369
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