Extrachromosomal recombination substrates recapitulate beyond 12/23 restricted VDJ recombination in nonlymphoid cells

Immunity. 2003 Jan;18(1):65-74. doi: 10.1016/s1074-7613(02)00507-1.

Abstract

V(D)J recombination occurs efficiently only between gene segments flanked by recombination signals (RSs) containing 12 and 23 base pair spacers (the 12/23 rule). A further limitation "beyond the 12/23 rule" (B12/23) exists at the TCRbeta locus and ensures Dbeta usage. Herein, we show that extrachromosomal V(D)J recombination substrates recapitulate B12/23 restriction in nonlymphoid cells. We further demonstrate that the Vbeta coding flank, the 12-RS heptamer/nonamer, and the 23-RS spacer each can significantly influence B12/23 restriction. Finally, purified core RAG1 and RAG2 proteins (together with HMG2) also reproduce B12/23 restriction in a cell-free system. Our findings indicate that B12/23 restriction of V(D)J recombination is cemented at the level of interactions between the RAG proteins and TCRbeta RS sequences.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • DNA-Binding Proteins / metabolism
  • Extrachromosomal Inheritance
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Genes, T-Cell Receptor beta*
  • Homeodomain Proteins / metabolism
  • In Vitro Techniques
  • Mice
  • Recombinant Fusion Proteins / metabolism
  • Recombination, Genetic*
  • TATA Box
  • Transfection

Substances

  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Rag2 protein, mouse
  • Recombinant Fusion Proteins
  • V(D)J recombination activating protein 2
  • RAG-1 protein