E2A and EBF act in synergy with the V(D)J recombinase to generate a diverse immunoglobulin repertoire in nonlymphoid cells

Mol Cell. 2000 Feb;5(2):343-53. doi: 10.1016/s1097-2765(00)80429-3.

Abstract

Immunoglobulin (Ig) and T cell receptor (TCR) genes are assembled during lymphocyte maturation through site-specific V(D)J recombination events. Here we show that E2A proteins act in concert with RAG1 and RAG2 to activate Ig VK1J but not Iglambda VlambdaIII-Jlambda1 rearrangement in an embryonic kidney cell line. In contrast, EBF, but not E2A, promotes VlambdaIII-Jlambda1 recombination. Either E2A or EBF activate IgH DH4J recombination but not V(D)J rearrangement. The Ig coding joints are diverse, contain nucleotide deletions, and lack N nucleotide additions. IgK VJ recombination requires the presence of the E2A transactivation domains. These observations indicate that in nonlymphoid cells a diverse Ig repertoire can be generated by the mere expression of the V(D)J recombinase and a transcriptional regulator.

Publication types

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

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA Nucleotidyltransferases / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Gene Rearrangement*
  • Genes, Immunoglobulin
  • Homeodomain Proteins / metabolism
  • Immunoglobulin G / genetics
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Joining Region / genetics
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin kappa-Chains / genetics
  • Immunoglobulins / genetics*
  • Kidney / cytology
  • Kidney / embryology
  • Kidney / physiology*
  • NF-kappa B / metabolism
  • Nuclear Proteins / metabolism
  • PAX5 Transcription Factor
  • Proto-Oncogene Proteins
  • Recombination, Genetic*
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • VDJ Recombinases

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Joining Region
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains
  • Immunoglobulins
  • NF-kappa B
  • Nuclear Proteins
  • PAX5 Transcription Factor
  • Proto-Oncogene Proteins
  • TCF3 protein, human
  • Trans-Activators
  • Transcription Factors
  • V(D)J recombination activating protein 2
  • proto-oncogene protein Spi-1
  • RAG-1 protein
  • DNA Nucleotidyltransferases
  • VDJ Recombinases