Hypermutation of immunoglobulin genes in memory B cells of DNA repair- deficient mice

  • 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 Te Riele
  • , Klaus Rajewsky

Research output: Contribution to journalArticleAcademicpeer-review

111 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1735-1742
Number of pages8
JournalJournal of Experimental Medicine
Volume187
Issue number11
DOIs
Publication statusPublished - 1 Jun 1998
Externally publishedYes

Keywords

  • DNA repair
  • DNA repair-deficient mice
  • Memory B cells
  • Naive B cells
  • Somatic mutations

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