Distinct signaling requirements for Dμ selection, IgH allelic exclusion, pre-B cell transition, and tumor suppression in B cell progenitors
Distinct signaling requirements for Dμ selection, IgH allelic exclusion, pre-B cell transition, and tumor suppression in B cell progenitors
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DOI：
10.1016/s1074-7613(03)00142-0
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发表时间：
2003-06-01
期刊：
影响因子：
32.4
通讯作者：
Kitamura, D
中科院分区：
文献类型：
--
作者：
Hayashi, K;Yamamoto, M;Kitamura, D
前B细胞受体启动前B细胞的扩张和分化(前B细胞转变)，以及抑制V-H到DJ(H)的重组(等位基因排斥)。后者也解释了表达DMU蛋白的Pro-B细胞的反选择(DMU选择)。然而，负责这些事件的信号通路仍然没有明确的定义。在这里，我们显示了Bash/CD19双突变小鼠在B细胞前转变时B细胞发育完全停止，表明两个B细胞特异性适配器部分冗余。在双突变小鼠中，等位基因排斥保持不变，而在Bash突变小鼠中，DMU，选择被取消。因此，这些事件需要不同的信号。此外，两只突变小鼠都死于前B细胞白血病，这表明Bash和CD19有助于抑制肿瘤。
The pre-B cell receptor triggers expansion and differentiation of pre-B cells (the pre-B cell transition), as well as inhibition Of V-H to DJ(H) recombination (allelic exclusion). The latter also accounts for counter-selection of pro-B cells expressing Dmu protein (Dmu selection). However, the signaling pathways responsible for these events remain poorly defined. Here we show complete arrest of B cell development at the pre-B cell transition in BASH/CD19 double mutant mice, indicating partial redundancy of the two B cell-specific adaptors. Allelic exclusion remained intact in the double mutant mice, whereas Dmu, selection was abolished in BASH mutant mice. Thus, distinct signals are required for these events. In addition, both mutant mice succumbed to pre-B cell leukemia, indicating that BASH and CD19 contribute to tumor suppression.