Promotion of V(D)J recombinational accessibility by the intronic E kappa element: role of the kappa B motif

Int Immunol. 1995 Dec;7(12):1995-2003. doi: 10.1093/intimm/7.12.1995.

Abstract

The accessibility of a chromosomally integrated TCR beta minilocus recombination substrate in a V(D)J recombinase-inducible cell line (HDR37) depends on incorporation of transcriptional enhancer elements such as the Ig kappa light chain intronic enhancer (E kappa). The E kappa element contains several functional motifs including the kappa B motif, which binds the NF-kappa B transcription factor. To assess molecular mechanisms by which E kappa promotes V(D)J recombinational accessibility, we compared the abilities of the wild-type E kappa, a corresponding E kappa sequence with a mutant kappa B motif (E kappa-kappa B-) and a kappa B motif dimer (kappa B2) to function in the context of the TCR beta minilocus/HDR37 system. The E kappa-containing minilocus underwent demethylation, transcription and V(D)J recombination, independently of copy number of integration site. Transfectants containing low copy numbers (one or two) of the E kappa-kappa B(-)-containing minilocus, like enhancerless or kappa B2-containing miniloci at any copy number, were inactive with respect to all three processes. In contrast, high-copy-number integrants of the E kappa-kappa B- substrates showed an integration-site dependent activation of all three processes. Together these data show that the kappa B motif plays a critical role in the ability of E kappa to confer V(D)J recombinational accessibility, but that it is not sufficient to mediate this process by itself.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • DNA / chemistry
  • DNA / genetics
  • DNA Nucleotidyltransferases / metabolism
  • DNA Primers / genetics
  • Enhancer Elements, Genetic
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Immunoglobulin kappa-Chains / genetics*
  • Introns
  • Methylation
  • Mice
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Recombination, Genetic*
  • Transfection
  • VDJ Recombinases

Substances

  • DNA Primers
  • Immunoglobulin kappa-Chains
  • Receptors, Antigen, T-Cell, alpha-beta
  • DNA
  • DNA Nucleotidyltransferases
  • VDJ Recombinases