Cutting edge: targeting of V beta to D beta rearrangement by RSSs can be mediated by the V(D)J recombinase in the absence of additional lymphoid-specific factors.
Assembly of TCRbeta variable region genes is ordered during thymocyte development with Dbeta to Jbeta rearrangement preceding Vbeta to DJbeta rearrangement. The 5'Dbeta 12-RSS is required to precisely and efficiently target Vbeta rearrangement beyond simply enforcing the 12/23 rule. By prohibiting direct Vbeta to Jbeta rearrangement, this restriction ensures Dbeta gene segment use in the assembly of essentially all TCRbeta variable region genes. In this study, we show that rearrangement of Vbeta 23-RSSs is significantly biased to the Dbeta 12-RSS over Jbeta 12-RSSs on extrachromosomal recombination substrates in nonlymphoid cells that express the recombinase-activating gene-1/2 proteins. These findings demonstrate that targeting of Vbeta to Dbeta rearrangement can be enforced by the V(D)J recombinase in the absence of lymphoid-specific factors other than the recombinase-activating gene-1/2 proteins.
Tillman
Robert E
RE
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
Wooley
Andrea L
AL
Khor
Bernard
B
Wehrly
Tara D
TD
Little
Carrie A
CA
Sleckman
Barry P
BP
D000818:Animals; D001667:Binding, Competitive / Q000235:genetics; D016466:CHO Cells / Q000201:enzymology / Q000276:immunology; D016384:Consensus Sequence; D006224:Cricetinae; D004254:DNA Nucleotidyltransferases / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D019674:Genes, T-Cell Receptor beta; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D007133:Immunoglobulin Joining Region / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D011995:Recombination, Genetic; D013379:Substrate Specificity / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045567:VDJ Recombinases
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases