To investigate the possible involvement of DNA repair in the process of somatic hypermutation of rearranged immunoglobulin variable (V) region genes, we have analyzed the occurrence, frequency, distribution, and pattern of mutations in rearranged Vλ1 light chain genes from naive and memory B cells in DNA repair–deficient mutant mouse strains. Hypermutation was found unaffected in mice carrying mutations in either of the following DNA repair genes: xeroderma pigmentosum complementation group (XP)A and XPD, Cockayne syndrome complementation group B (CSB), mutS homologue 2 (MSH2), radiation sensitivity 54 (RAD54), poly (ADP-ribose) polymerase (PARP), and 3-alkyladenine DNA-glycosylase (AAG). These results indicate that both subpathways of nucleotide excision repair, global genome repair, and transcription-coupled repair are not required for somatic hypermutation. This appears also to be true for mismatch repair, RAD54-dependent double-strand–break repair, and AAG-mediated base excision repair.
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1 June 1998
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June 01 1998
Hypermutation of Immunoglobulin Genes in Memory B Cells of DNA Repair–deficient Mice
Heinz Jacobs,
Heinz Jacobs
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Yosho Fukita,
Yosho Fukita
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Gijsbertus T.J. van der Horst,
Gijsbertus T.J. van der Horst
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Jan de Boer,
Jan de Boer
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Geert Weeda,
Geert Weeda
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Jeroen Essers,
Jeroen Essers
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Niels de Wind,
Niels de Wind
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Bevin P. Engelward,
Bevin P. Engelward
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Leona Samson,
Leona Samson
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Sjef Verbeek,
Sjef Verbeek
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Josiane Ménissier de Murcia,
Josiane Ménissier de Murcia
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Gilbert de Murcia,
Gilbert de Murcia
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Hein t e Riele,
Hein t e Riele
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Klaus Rajewsky
Klaus Rajewsky
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
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Heinz Jacobs
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Yosho Fukita
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Gijsbertus T.J. van der Horst
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Jan de Boer
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Geert Weeda
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Jeroen Essers
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Niels de Wind
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Bevin P. Engelward
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Leona Samson
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Sjef Verbeek
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Josiane Ménissier de Murcia
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Gilbert de Murcia
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Hein t e Riele
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Klaus Rajewsky
From the *Basel Institute for Immunology, CH-4005 Basel, Switzerland; the ‡Institute for Genetics, University of Cologne, 50931 Cologne, Germany; the §Department of Cellular Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands; the ‖Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; the ¶Department of Immunology, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands; the **Ecole Superieure de Biotechnologie de Strasbourg, Université Louis Pasteur, F-67400 Illkirch-Graffenstaden, France; and the ††Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115
Address correspondence to Heinz Jacobs, Basel Institute for Immunology, Grenzacherstr. 487, CH-4005 Basel, Switzerland. Phone: 41-61-6051281; Fax: 41-61-6051364; E-mail: [email protected]
Received:
December 01 1997
Revision Received:
February 23 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 187 (11): 1735–1743.
Article history
Received:
December 01 1997
Revision Received:
February 23 1998
Citation
Heinz Jacobs, Yosho Fukita, Gijsbertus T.J. van der Horst, Jan de Boer, Geert Weeda, Jeroen Essers, Niels de Wind, Bevin P. Engelward, Leona Samson, Sjef Verbeek, Josiane Ménissier de Murcia, Gilbert de Murcia, Hein t e Riele, Klaus Rajewsky; Hypermutation of Immunoglobulin Genes in Memory B Cells of DNA Repair–deficient Mice . J Exp Med 1 June 1998; 187 (11): 1735–1743. doi: https://doi.org/10.1084/jem.187.11.1735
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