Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo

Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo
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DOI:
10.1038/ni1075
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发表时间:
2004-06-01
期刊:
影响因子:
30.5
通讯作者:
Owen, MJ
Owen, MJ
中科院分区:
医学1区
文献类型:
--
作者:
Hozumi, K;Negishi, N;Owen, MJ

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Notch受体及其配体参与许多发育系统,但它们在出生后如何发挥作用尚不清楚,因为它们的无效突变体在胚胎发生期间会产生严重的缺陷。在这里,我们使用Cre-loxP系统删除的Delta样1基因(Dll 1)出生后,并证明了脾边缘带B细胞在Dll 1-null小鼠完全消失。相反,T细胞发育不受影响。这些结果表明,Dll 1在T细胞-B细胞发育的分支点上作为Notch 1的配体是必需的,但对于边缘区B细胞的产生是必需的。因此,Notch信号传导对于体内淋巴细胞发育是必不可少的,但是存在可以驱动胸腺内T细胞发育的Notch-Notch配体信号传导的冗余。
Notch receptors and their ligands contribute to many developmental systems, but it is not apparent how they function after birth, as their null mutants develop severe defects during embryogenesis. Here we used the Cre-loxP system to delete the Delta-like 1 gene (Dll1) after birth and demonstrated the complete disappearance of splenic marginal zone B cells in Dll1-null mice. In contrast, T cell development was unaffected. These results demonstrated that Dll1 was dispensable as a ligand for Notch1 at the branch point of T cell-B cell development but was essential for the generation of marginal zone B cells. Thus, Notch signaling is essential for lymphocyte development in vivo, but there is a redundancy of Notch-Notch ligand signaling that can drive T cell development within the thymus.