c-Myb is critical for B cell development and maintenance of follicular B cells
c-Myb is critical for B cell development and maintenance of follicular B cells
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DOI：
10.1016/j.immuni.2005.08.005
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发表时间：
2005-09-01
期刊：
影响因子：
32.4
通讯作者：
Bender, TP
中科院分区：
文献类型：
--
作者：
Thomas, MD;Kremer, CS;Bender, TP
c-Myb转录因子在最终造血过程中起着至关重要的作用。然而，Myb传统零突变的胚胎致死性阻碍了对淋巴细胞中c-Myb功能的分析。通过对Myb基因座进行组织特异性失活，我们发现Myb基因的缺失会导致B细胞从原B细胞向前B细胞转变过程中的部分阻滞，从而导致骨髓中新B细胞的输出大大减少。此外，我们证明Myb对脾B细胞的增殖并不是必需的，但由于脾B细胞存活率降低，c-Myb功能的丧失会阻止正常的B细胞稳态。生存降低伴随着对B细胞生存因子BLyS（也称为BAFF）的低反应性，BLyS受体3 （BR3）的表达降低以及PKC三角洲核积累的调节改变。因此，c-Myb在b淋巴生成的多个阶段都很重要。
The c-Myb transcription factor is crucial during definitive hematopoiesis. However, the embryonic lethality of Myb traditional null mutations has precluded analysis of c-Myb function in lymphocytes. Using tissue-specific inactivation at the Myb locus, we demonstrate that loss of Myb causes a partial block during B cell development at the pro-B to pre-B cell transition, resulting in greatly decreased output of new B cells from the bone marrow. Furthermore, we demonstrate that Myb is not essential for the proliferation of splenic B cells, but that loss of c-Myb function prevents normal B cell homeostasis due to decreased splenic B cell survival. Decreased survival is accompanied by hyporesponsiveness to the B cell survival factor BLyS (also termed BAFF), decreased expression of the BLyS receptor 3 (BR3), and altered regulation of PKC delta nuclear accumulation. Thus, c-Myb is important during multiple stages of B-lymphopoiesis.