Critical roles for c-Myb in lymphoid priming and early B-cell development
Critical roles for c-Myb in lymphoid priming and early B-cell development
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DOI：
10.1182/blood-2009-08-239210
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发表时间：
2010-04-08
期刊：
影响因子：
20.3
通讯作者：
Nutt, Stephen L.
中科院分区：
文献类型：
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作者：
Greig, Kylie T.;de Graaf, Carolyn A.;Nutt, Stephen L.
c-Myb是在许多造血谱系中具有功能的转录因子。c-MyB缺陷小鼠显示B细胞数量减少;然而，由于在B细胞谱系中未鉴定出关键靶基因，因此c-MyB在B淋巴细胞生成中的作用尚不清楚。我们证明了在B细胞祖细胞中c-Myb的条件性缺失完全废除了B细胞发育。c-MyB是淋巴祖细胞对细胞因子白细胞介素-7和胸腺基质淋巴细胞生成素应答所必需的;在缺乏足够的c-MyB活性的情况下，小鼠表现出与在白细胞介素-7受体α缺陷动物中观察到的非常相似的B淋巴细胞减少症。多能祖细胞区室的分析表明，c-Myb也需要多个淋巴相关基因的上调，包括IL 7 r，并为共同的淋巴祖细胞群体的后续发展。这些数据表明，c-Myb在控制淋巴细胞特化和早期B细胞分化的调节途径中起着关键作用。（血。2010; 115（14）：2796-2805）
c-Myb is a transcription factor with functions in many hematopoietic lineages. c-Myb-deficient mice display reduced numbers of B cells; however, it is unknown what role c-Myb plays in B lymphopoiesis because no critical target genes have been identified in the B-cell lineage. We demonstrate that conditional deletion of c-Myb in B-cell progenitors completely abolishes B-cell development. c-Myb is required for lymphoid progenitors to respond to the cytokines interleukin-7 and thymic stromal lymphopoietin; in the absence of sufficient c-Myb activity, mice display a B lymphopenia that closely resembles that observed in interleukin-7 receptor alpha-deficient animals. Analysis of the multipotent progenitor compartment indicates that c-Myb is also required for up-regulation of multiple lymphoidassociated genes, including Il7r, and for the subsequent development of the common lymphoid progenitor population. These data show that c-Myb plays a critical role in the regulatory pathways governing lymphoid specification and early B-cell differentiation. (Blood. 2010; 115(14): 2796-2805)