Limited effect of chromatin remodeling on D(beta)-to-J(beta) recombination in CD4+CD8+ thymocyte: implications for a new aspect in the regulation of TCR beta gene recombination.
We have generated mutant mice in which TCR beta chain enhancer (E(beta)) was replaced with the TCR alpha chain enhancer (E(alpha)). Using this mouse model, we analyzed (i) recombination status of the TCR beta chain genes after functional V(D)J rearrangements occurred in the first allele during double-negative (DN)-to-double-positive (DP) transition and (ii) involvement of E(beta) for the expression of rearranged TCR beta chain genes. Our data show that E(alpha) substituted for E(beta) function to express a similar extent of TCR beta chains exactly at the same time as did E(beta) (CD25+CD44- DN stage), although the proportion of TCR beta+ cells at this stage was low in mutant mice. At the DP stage, germline transcription and histone acetylation of D(beta)-J(beta) loci were detectable at a high degree in both mutant and wild-type mice. However, DP cells in mutant mice retained the germline D(beta)-J(beta) configuration at a higher frequency than that of wild-type mice, whereas both DP cells expressed TCR beta chains to a similar extent. These data suggest that chromatin opening has a limited impact on D(beta)-to-J(beta) recombination at the DP stage and that E(alpha) is functionally equivalent to E(beta) in promoting expression of functionally rearranged TCR beta chain genes through DN-to-DP transition.
Senoo
M
M
Department of Immunology, Tokai University School of Medicine, Bouseidai, Isehara, Kanagawa 259-1193, Japan.
Mochida
N
N
Wang
L
L
Matsumura
Y
Y
Suzuki
D
D
Takeda
N
N
Shinkai
Y
Y
Habu
S
S
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002843:Chromatin / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D018095:Germ-Line Mutation; D051379:Mice; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D011995:Recombination, Genetic; D013950:Thymus Gland / Q000276:immunology*
D002843:Chromatin; D016693:Receptors, Antigen, T-Cell, alpha-beta