A20 and CYLD Do Not Share Significant Overlapping Functions during B Cell Development and Activation
A20 and CYLD Do Not Share Significant Overlapping Functions during B Cell Development and Activation
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DOI：
10.4049/jimmunol.1200396
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发表时间：
2012-11-01
影响因子：
4.4
通讯作者：
Schmidt-Supprian, Marc
中科院分区：
文献类型：
--
作者：
Chu, Yuanyuan;Soberon, Valeria;Schmidt-Supprian, Marc
泛素编辑酶A20（TNFAIP 3）和去泛素化酶CYLD是NF-κ B信号传导的中心负调节因子。两者都可以通过从一组重叠的信号分子中去除非蛋白水解的K63连接的多聚泛素链来起作用。在B细胞中，A20缺乏导致活动过度、免疫稳态丧失、炎症和自身免疫。报道的CYLD缺乏的后果是有争议的，从没有影响到戏剧性的B细胞增生。这些差异可能是由于A20对CYLD功能丧失的补偿不同。因此，为了探索A20和CYLD之间潜在的重叠生理功能，我们产生并表征了A20/CYLD双缺陷B细胞。有趣的是，缺乏A20和CYLD并没有加剧A20缺陷型B细胞的发育缺陷和高反应活性。此外，在体外用抗-CD 40、LPS和CpG刺激后，B细胞活化的程度在缺乏A20/CYLD的B细胞和单独的A20中相当。然而，响应于BCR交联，我们观察到A20和CYLD缺乏的小但可再现的加性效应。综上所述，我们的结果表明，A20和CYLD在B细胞发育和活化过程中没有共同的重要功能。免疫学杂志，2012，189：4437-4443。
The ubiquitin-editing enzyme A20 (TNFAIP3) and the deubiquitinase CYLD are central negative regulators of NF-kappa B signaling. Both can act by removing nonproteolytic K63-linked polyubiquitin chains from an overlapping set of signaling molecules. In B cells, A20 deficiency results in hyperactivity, loss of immune homeostasis, inflammation, and autoimmunity. The reported consequences of CYLD deficiency are controversial, ranging from an absence of effects to dramatic B cell hyperplasia. These differences could be due to varying compensation for the loss of CYLD function by A20. Therefore, to explore potential overlapping physiological functions between A20 and CYLD, we generated and characterized A20/CYLD double-deficient B cells. Interestingly, the lack of both A20 and CYLD did not exacerbate the developmental defects and hyperresponsive activity of A20-deficient B cells. In addition, the extent of B cell activation after in vitro stimulation with anti-CD40, LPS, and CpG was comparable in B cells lacking A20/CYLD and A20 alone. However, in response to BCR cross-linking, we observed small but reproducible additive effects of the lack of A20 and CYLD. Taken together, our results demonstrate that A20 and CYLD do not share significant functions during B cell development and activation. The Journal of Immunology, 2012, 189: 4437-4443.