A pivotal role for DNase I-sensitive regions 3b and/or 4 in the induction of somatic hypermutation of IgH genes

A. Terauchi, K. Hayashi, D. Kitamura, Y. Kozono, N. Motoyama, T. Azuma

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31 Citations (Scopus)

Abstract

Chimeric mice were prepared from embryonic stem cells transfected with IgH genes as transgenes and RAG-2-deficient blastocysts for the purpose of identifying the cis-acting elements responsible for the induction of somatic hypermutation. Among the three transgene constructs used, the VH promoter, the rearranged VH-D-JH, an intron enhancer/matrix attachment region, and human Cμ were common to all, but the 3′-untranslated region in each construct was different. After immunization of mice with a T cell-dependent Ag, the distribution and frequency of hypermutation in transgenes were analyzed. The transgene lacking the 3′ untranslated region showed a marginal degree of hypermutation. Addition of the 3′ enhancer resulted in a slight increase in the number of mutations. However, the transgene containing DNase I-sensitive regions 3b and 4 in addition to the 3′ enhancer showed more than a 10-fold increase in hypermutation, reaching levels comparable to those observed in endogenous VH186.2 genes of C57BL/6 mice.

Original languageEnglish
Pages (from-to)811-820
Number of pages10
JournalJournal of Immunology
Volume167
Issue number2
DOIs
Publication statusPublished - Jul 15 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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