The "dispensable" portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development

Hong Erh Liang, Lih Yun Hsu, Dragana Cado, Lindsay G. Cowell, Garnett Kelsoe, Mark S. Schlissel

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

Previous in vitro studies defined the minimal regions of RAG1 and RAG2 essential for V(D)J recombination. In order to characterize the role of the C-terminal "dispensable" portion of RAG2, we generated core-RAG2 knock-in mice. We found that the core-RAG2-containing recombinase complex is selectively defective in catalyzing V-to-DJ rearrangement at the IgH and TCRβ loci, resulting in partial developmental blocks in B and T lymphopoiesis. Analysis of recombination intermediates showed defects at the cleavage phase of the reaction. We also observed a reduction in overall recombinase activity in core-RAG2-expressing thymocytes, leading us to suggest that the interaction of a defective recombinase with RSS sequences unique to VH and Vβ gene segments may underlie the specific V-to-DJ rearrangement defect in core-RAG2 mice.

Original languageEnglish (US)
Pages (from-to)639-651
Number of pages13
JournalImmunity
Volume17
Issue number5
DOIs
StatePublished - Nov 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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