title: E2A and EBF act in synergy with the V(D)J recombinase to generate a diverse immunoglobulin repertoire in nonlymphoid cells.
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.
authors.affiliation: Department of Biology, University of California, San Diego, La Jolla 92093, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Romanow
authors.forename: A W
authors.initials: AW
authors.lastname: Langerak
authors.forename: P
authors.initials: P
authors.lastname: Goebel
authors.forename: I L
authors.initials: IL
authors.lastname: Wolvers-Tettero
authors.forename: J J
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: A J
authors.initials: AJ
authors.lastname: Feeney
authors.forename: C
authors.initials: C
authors.lastname: Murre
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins; D004254:DNA Nucleotidyltransferases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D018398:Homeodomain Proteins / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics*; D007668:Kidney / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D051757:PAX5 Transcription Factor; D011518:Proto-Oncogene Proteins; D011995:Recombination, Genetic; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D045567:VDJ Recombinases; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004254:DNA Nucleotidyltransferases; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007136:Immunoglobulins; D016328:NF-kappa B; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D045567:VDJ Recombinases; D000099232:Proto-Oncogene Protein Spi-1; C407909:TCF3 protein, human; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein