B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors.
B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors.
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DOI：
10.1084/jem.20031800
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发表时间：
2004-02-16
影响因子：
15.3
通讯作者：
Gerstein, RM
中科院分区：
文献类型：
--
作者：
Borghesi, L;Hsu, LY;Miller, JP;Anderson, M;Herzenberg, L;Herzenberg, L;Schlissel, MS;Allman, D;Gerstein, RM
在发育中的淋巴细胞中表达V(D)J重组酶活性是启动V(D)J在抗原受体基因座上重组所必需的。然而，目前尚不清楚V(D)J重组酶在造血发育过程中何时首次激活，也不知道是什么因素激活了多能造血祖细胞中的重组酶。使用表达荧光转基因V(D)J重组报告的小鼠，我们发现V(D)J重组酶早在普通淋巴系祖细胞(CLP)中就活跃，但在保留髓系血统潜力的上游祖细胞中不活跃。在所有四个子代谱系(B、T、NK和DC)中都可以检测到这种重组酶活性的证据，并且在紧邻CLP下游的祖细胞亚群中，RAG2的水平最高。通过单细胞聚合酶链式反应，我们证明在5%的脾自然杀伤细胞中可以在∼基因的IgH位点检测到V(D)J重排。最后，我们发现在CLP中重组酶的活性在很大程度上受ERAG增强子的控制。由于ERAG增强子的活性仅限于B细胞谱系，这为在多能祖细胞中建立谱系特异性转录程序提供了第一个分子证据。
Expression of V(D)J recombinase activity in developing lymphocytes is absolutely required for initiation of V(D)J recombination at antigen receptor loci. However, little is known about when during hematopoietic development the V(D)J recombinase is first active, nor is it known what elements activate the recombinase in multipotent hematopoietic progenitors. Using mice that express a fluorescent transgenic V(D)J recombination reporter, we show that the V(D)J recombinase is active as early as common lymphoid progenitors (CLPs) but not in the upstream progenitors that retain myeloid lineage potential. Evidence of this recombinase activity is detectable in all four progeny lineages (B, T, and NK, and DC), and rag2 levels are the highest in progenitor subsets immediately downstream of the CLP. By single cell PCR, we demonstrate that V(D)J rearrangements are detectable at IgH loci in ∼5% of splenic natural killer cells. Finally, we show that recombinase activity in CLPs is largely controlled by the Erag enhancer. As activity of the Erag enhancer is restricted to the B cell lineage, this provides the first molecular evidence for establishment of a lineage-specific transcription program in multipotent progenitors.
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影响因子：
16
作者：
Grawunder, U;Zimmer, D;Lieber, MR
通讯作者：
Lieber, MR
影响因子：
32.4
作者：
Igarashi, H;Gregory, SC;Kincade, PW
通讯作者：
Kincade, PW
影响因子：
32.4
作者：
GRAWUNDER, U;LEU, TMJ;WINKLER, TH
通讯作者：
WINKLER, TH
影响因子：
32.4
作者：
Hsu, LY;Lauring, J;Schlissel, MS
通讯作者：
Schlissel, MS
影响因子：
4.4
作者：
Corcoran, L;Ferrero, I;Shortman, K
通讯作者：
Shortman, K