Stadanlick Jason E, Kaileh Mary, Karnell Fredrick G, Scholz Jean L, Miller Juli P, Quinn William J, Brezski Randall J, Treml Laura S, Jordan Kimberly A, Monroe John G, Sen Ranjan, Cancro Michael P
Deparment of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Nat Immunol. 2008 Dec;9(12):1379-87. doi: 10.1038/ni.1666. Epub 2008 Nov 2.
The survival of transitional and mature B cells requires both the B cell antigen receptor (BCR) and BLyS receptor 3 (BR3), which suggests that these receptors send signals that are nonredundant or that engage in crosstalk with each other. Here we show that BCR signaling induced production of the nonclassical transcription factor NF-kappaB pathway substrate p100, which is required for transmission of BR3 signals and thus B cell survival. The capacity for sustained p100 production emerged during transitional B cell differentiation, the stage at which BCR signals begin to mediate survival rather than negative selection. Our findings identify a molecular mechanism for the reliance of primary B cells on continuous BR3 and BCR signaling, as well as for the gradual resistance to negative selection that is acquired during B cell maturation.
过渡性和成熟B细胞的存活需要B细胞抗原受体（BCR）和B淋巴细胞刺激因子受体3（BR3），这表明这些受体发出的信号是非冗余的，或者它们之间存在相互作用。在这里，我们表明BCR信号诱导非经典转录因子NF-κB途径底物p100的产生，这是BR3信号传递以及B细胞存活所必需的。持续产生p100的能力在过渡性B细胞分化过程中出现，在这个阶段BCR信号开始介导存活而不是负选择。我们的研究结果确定了一个分子机制，解释了原代B细胞对持续BR3和BCR信号的依赖，以及B细胞成熟过程中逐渐获得的对负选择的抗性。
