A checkpoint in B-lymphopoiesis related to Notch resistance
A checkpoint in B-lymphopoiesis related to Notch resistance
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与 Notch 抵抗相关的 B 淋巴细胞生成检查点
DOI：
10.1016/j.bbrc.2011.11.072
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
奥山一生
中科院分区：
文献类型：
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作者：
Teruhide Koyama;Takayuki Sakurai;Akiko Kamiyoshi;Yuka Shindo;Takuma Arai;Yasuhiro Iesato;Lei Yang;Takahiro Yoshizawa;Ryuichi Uetake;Akihiro Yamauchi;Megumu Tanaka;Takayuki Shindo;奥山一生
虽然小鼠 B 淋巴细胞和 T 淋巴细胞生成需要重叠的分子，但它们分别发生在不同的器官中：骨髓 (BM) 和胸腺。由于 Notch1 与 delta 样配体 (Dll) 的相互作用不足，BM 微环境无法支持 T 淋巴细胞生成。 Notch1/Dll 相互作用也在胸腺 B 淋巴细胞生成的抑制中发挥作用。然而，目前尚不清楚 Notch1/Dll 相互作用是否可以单独解释为什么胸腺不支持 B 淋巴细胞生成。在这项研究中，我们通过在表达丰富 Dll1 的基质细胞上培养胸腺中的前体群体与 BM 中的前体群体进行比较。我们证明Flt3+Il7r+B220+Cd19+BM细胞在此条件下产生B细胞。我们将它们定义为对 Dll1 具有抵抗力。在胸腺中，检测不到 Dll1 抗性细胞。这表明 Dll1 抗性细胞的缺失可能解释了胸腺中 B 淋巴细胞生成的缺失。
While murine B- and T-lymphopoiesis require overlapping molecules, they occur in separate organs: the bone marrow (BM) and the thymus, respectively. The BM microenvironment is incapable of supporting T-lymphopoiesis because of insufficient interactions of Notch1 with delta-like ligand (Dll). Notch1/Dll interactions also play a role in the suppression of B-lymphopoiesis in the thymus. However, it is still unclear whether the Notch1/Dll interaction alone explains why the thymus does not support B-lymphopoiesis. In this study, we compared the precursor population colonizing the thymus with that in the BM by culturing them on stromal cells expressing abundant Dll1. We demonstrated that Flt3+Il7r+B220+Cd19+BM cells gave rise to B cells under this condition. We defined them as resistant to Dll1. In the thymus, Dll1-resistant cells were undetectable. This suggested that the absence of Dll1-resistant cells might explain the absence of B-lymphopoiesis in the thymus.