Open AccessThe T cell receptor β enhancer promotes access and pairing of Dβ and Jβ gene segments during V(D)J recombination
Author(s) -
Chun Jeih Ryu,
Brian B. Haines,
Dobrin Draganov,
Yun Hee Kang,
Charles E. Whitehurst,
Tara Schmidt,
Hyo Jeong Hong,
Jianzhu Chen
Publication year - 2003
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2235807100
Subject(s) - enhancer , v(d)j recombination , gene rearrangement , cleavage (geology) , biology , gene , cd8 , recombination , pairing , t cell receptor , microbiology and biotechnology , genetics , t cell , gene expression , physics , antigen , paleontology , superconductivity , immune system , quantum mechanics , fracture (geology)
The precise function of cis elements in regulating V(D)J recombination is still controversial. Here, we determined the effect of inactivation of the TCRbeta enhancer (Ebeta) on cleavage and rearrangement of Dbeta1, Dbeta2, Jbeta1, and Jbeta2 gene segments in CD4-CD8- [double-negative (DN)] and CD4+CD8+ [double-positive (DP)] thymocytes. In Ebeta-deficient mice, (i) Dbeta1 rearrangements were more severely impaired than Dbeta2 rearrangements; (ii) most of the Dbeta and Jbeta cleavages and rearrangements occurred in DP, rather than in DN, thymocytes; and (iii) most of the 3' Dbeta1 cleavages were coupled to 5' Dbeta2 cleavages instead of to Jbeta cleavages, resulting in nonstandard Dbeta1-Dbeta2-Jbeta2 joints. These findings suggest that the Ebeta regulates TCRbeta rearrangement by promoting accessibility of Dbeta and Jbeta gene segments in DN thymocytes and proper pairing between Dbeta1 and Jbeta gene segments for cleavage and joining in DP thymocytes.