Differential regulation of proximal and distal Vbeta segments upstream of a functional VDJbeta1 rearrangement upon beta-selection.
Differential regulation of proximal and distal Vbeta segments upstream of a functional VDJbeta1 rearrangement upon beta-selection.
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DOI：
10.4049/jimmunol.1101079
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发表时间：
2011-09-15
期刊：
影响因子：
--
通讯作者：
Bassing CH
中科院分区：
文献类型：
--
作者：
Brady BL;Bassing CH
Developmental stage specific regulation of transcriptional accessibility helps control V(D)J recombination. Vβ segments on unrearranged TCRβ alleles are accessible in CD4−/CD8− (double-negative [DN]) thymocytes, when they recombine, and inaccessible in CD4+/CD8+ (double-positive [DP]) thymocytes, when they do not rearrange. Down-regulation of Vβ accessibility on unrearranged alleles is linked with Lat-dependent β-selection signals that inhibit Vβ rearrangement, stimulate Ccnd3-driven proliferation, and promote DN-to-DP differentiation. Transcription and recombination of Vβs on VDJβ-rearranged alleles in DN cells has not been studied; Vβs upstream of functional VDJβ-rearrangements have been found to remain accessible, yet not recombine, in DP cells. To elucidate contributions of β-selection signals in regulating Vβ transcription and recombination on VDJβ-rearranged alleles, we analyzed wild-type (WT), Ccnd3−/−, and Lat−/− mice containing a preassembled functional Vβ1DJCβ1 (Vβ1NT) gene. Vβ10 segments located just upstream of this VDJCβ1 gene were the predominant germline Vβs that rearranged in Vβ1NT/NT and Vβ1NT/NTCcnd3−/− thymocytes, while Vβ4 and Vβ16 segments located further upstream rearranged at similar levels as Vβ10 in Vβ1NT/NTLat−/− DN cells. We previously showed that Vβ4 and Vβ16, but not Vβ10, are transcribed on Vβ1NT alleles in DP thymocytes; we now demonstrate that Vβ4, Vβ16, and Vβ10 are transcribed similar levels in Vβ1NT/NTLat−/− DN cells. These observations indicate that suppression of Vβ rearrangements is not dependent upon Ccnd3-driven proliferation, and DN residence can influence the repertoire of Vβs that recombine on alleles containing an assembled VDJCβ1 gene. Our findings also reveal that β-selection can differentially silence rearrangement of germline Vβ segments located proximal and distal to functional VDJβ genes.
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影响因子：
30.5
作者：
Jackson, A;Kondilis, HD;Krangel, MS
通讯作者：
Krangel, MS
影响因子：
10.5
作者：
Hoffman, ES;Passoni, L;Hayday, AC
通讯作者：
Hayday, AC
影响因子：
4.4
作者：
Hozumi, K;Kobori, A;Habu, S
通讯作者：
Habu, S
影响因子：
2.7
作者：
LEBER, BF;AMLOT, P;NORTON, JD
通讯作者：
NORTON, JD
DOI：
10.1084/jem.192.5.625
发表时间：
2000-09-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mathieu N;Hempel WM;Spicuglia S;Verthuy C;Ferrier P
通讯作者：
Ferrier P