Stat5 is essential for early B cell development but not for B cell maturation and function
Stat5 is essential for early B cell development but not for B cell maturation and function
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DOI：
10.4049/jimmunol.179.2.1068
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发表时间：
2007-07-15
影响因子：
4.4
通讯作者：
Wang, Demin
中科院分区：
文献类型：
--
作者：
Dai, Xuezhi;Chen, Yuhong;Wang, Demin
这两个密切相关的Stat5蛋白(Stat5a和Stat5b)被广泛的细胞因子激活。然而，随着Stat5a/5B参与干细胞功能的复杂化，Stat5a/513在淋巴细胞尤其是B细胞的发育和功能中的作用还不完全清楚。在这项研究中，我们证明了Stat5a/5B(-/-)胎肝细胞有严重的B细胞祖细胞减少，但明显有髓系祖细胞。在致死照射的野生型或JAK3(-/-)小鼠中，突变的胎肝细胞可以产生造血祖细胞和髓系细胞，但不能产生前B细胞祖细胞以外的B细胞。Stat5a/513基因缺失在体外直接损害了IL-7介导的B细胞增殖。值得注意的是，将Stat5a重新导入Stat5a/513(-/-)胎肝细胞，恢复了它们发育B细胞的能力。重要的是，CD19-Cre介导的B细胞室中Stat5a/513的缺失特异性地损害了B细胞的早期发育，但不影响B细胞的晚期成熟。此外，B细胞特异性缺失的Stat5a/5B不会损害脾B细胞的存活、增殖和Ig的产生。综上所述，这些数据表明，Stat5a/5B直接控制IL-7介导的早期B细胞发育，但不是B细胞成熟和Ig产生所必需的。
The two closely related Stat5 (Stat5A and Stat5B) proteins are activated by a broad spectrum of cytokines. However, with the complication of the involvement of Stat5A/5B in stem cell function, the role of Stat5A/513 in the development and function of lymphocytes, especially B cells, is not fully understood. In this study, we demonstrated that Stat5A/5B(-/-) fetal liver cells had severe diminution of B cell progenitors but clearly had myeloid progenitors. Consistently, the mutant fetal liver cells could give rise to hemopoietic progenitors and myeloid cells but not B cells beyond pro-B cell progenitors in lethally irradiated wild-type or Jak3(-/-) mice. Deletion of Stat5A/513 in vitro directly impaired IL-7-mediated B cell expansion. Of note, reintroduction of Stat5A back into Stat5A/513(-/-) fetal liver cells restored their abilities to develop B cells. Importantly, CD19-Cre-mediated deletion of Stat5A/513 in the B cell compartment specifically impaired early B cell development but not late B cell maturation. Moreover, the B cell-specific deletion of Stat5A/5B did not impair splenic B cell survival, proliferation, and Ig production. Taken together, these data demonstrate that Stat5A/5B directly control IL-7-mediated early B cell development but are not required for B cell maturation and Ig production.