Canonical NF-κB activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation
Canonical NF-κB activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation
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DOI：
10.1016/j.immuni.2006.04.005
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发表时间：
2006-06-01
期刊：
影响因子：
32.4
通讯作者：
Schmidt-Supprian, Marc
中科院分区：
文献类型：
--
作者：
Sasaki, Yoshiteru;Derudder, Emmanuel;Schmidt-Supprian, Marc
成熟B细胞的维持依赖于BAFF-R细胞表面受体发出的信号，但这些信号的性质还不完全清楚。通过消除基本支架蛋白NEW抑制经典NF-κ B转录因子活性，可将B细胞发育阻滞在与BAFF-R缺乏相同的阶段。相应地，通过组成型活性I κ B激酶2激活该途径使得B细胞存活不依赖于BAFF-R：BAFF相互作用，并阻止促凋亡PKC 8核转位。此外，经典NF-κ B活性介导的分化和适当的定位滤泡和边缘区B细胞在BAFF-R的情况下，但不是CD 19。通过取代BAFF-R信号，组成型典型NF-κ B信号传导（各种B细胞淋巴瘤的标志）引起静息B细胞的积累并促进它们在活化后的增殖和存活，但本身不诱导淋巴瘤发生。因此，在B细胞发育和发病机制中，典型的NF-κ B活性可以替代BAFF-R信号。
The maintenance of mature B cells hinges on signals emitted from the BAFF-R cell-surface receptor, but the nature of these signals is incompletely understood. Inhibition of canonical NF-kappa B transcription factor activity through ablation of the essential scaffold protein NEW arrests B cell development at the same stage as BAFF-R deficiency. Correspondingly, activation of this pathway by constitutively active I kappa B Kinase2 renders B cell survival independent of BAFF-R:BAFF interactions and prevents proapoptotic PKC8 nuclear translocation. In addition, canonical NF-kappa B activity mediates differentiation and proper localization of follicular and marginal zone B cells in the absence of BAFF-R, but not CD19. By replacing BAFF-R signals, constitutive canonical NF-kappa B signaling, a hallmark of various B cell lymphomas, causes accumulation of resting B cells and promotes their proliferation and survival upon activation, but does not per se induce lymphomagenesis. Therefore, canonical NF-kappa B activity can substitute for BAFF-R signals in B cell development and pathogenesis.