Receptors, subcellular compartments and the regulation of peripheral B cell responses: the illuminating state of anergy.
Receptors, subcellular compartments and the regulation of peripheral B cell responses: the illuminating state of anergy.
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DOI：
10.1016/j.molimm.2010.10.024
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发表时间：
2011-06
影响因子：
3.6
通讯作者：
Veselits M
中科院分区：
文献类型：
--
作者：
Clark MR;Tanaka A;Powers SE;Veselits M
通过B细胞抗原受体（BCR）的信号对于细胞活化是必要的，但不是充分的。共刺激信号必须通过其他免疫识别受体系统提供，如MHC II类/CD 40和Toll样受体（TLR）9，其只能在特化晚期内体（含有MHC II类的隔室或MIIC）的进行性环境中有效地获得其配体。长期以来人们已经认识到，BCR通过有效地捕获复合抗原并将它们递送至晚期内体，是细胞表面上的活化事件与依赖于晚期内体的活化事件之间的联系。然而，越来越明显的是，BCR还指导II类MHC和TLR 9易位到MIIC中，并且这些受体的内吞流动与BCR的内吞流动一致。这可能确保受体复合物在MIIC内的紧密并置以及配体从BCR到MHC II类和TLR 9的有效转移。受体内吞运动的这种复杂协调依赖于通过BCR引起的信号的质量。不能激活特异性信号传导途径，例如在无反应性B细胞中发生的，阻止BCR和TLR 9进入MIIC并消除TLR 9激活。像无反应性一样，这种内吞运输的阻断是迅速可逆的。这些发现表明，细胞反应性可以通过控制重要免疫识别受体的亚细胞位置的机制来确定。
Signals through the B cell antigen receptor (BCR) are necessary but not sufficient for cellular activation. Co-stimulatory signals must be provided through other immune recognition receptor systems, such as MHC class II/CD40 and the toll-like receptor (TLR) 9 that can only productively acquire their ligands in the processive environment of specialized late endosomes (MHC class II containing compartment or MIIC). It has long been appreciated that the BCR, by effectively capturing complex antigens and delivering them to late endosomes, is the link between activation events on the cell surface and those dependent on late endosomes. However, it has become increasingly apparent that the BCR also directs the translocation of MHC class II and TLR9 into the MIIC and that the endocytic flow of these receptors coincides with that of the BCR. This likely ensures close apposition of receptor complexes within the MIIC and the efficient transfer of ligands from the BCR to MHC class II and TLR9. This complex orchestration of receptor endocytic movement is dependent upon the quality of signals elicited through the BCR. Failure to activate specific signaling pathways, such as occurs in anergic B cells, prevents the entry of the BCR and TLR9 into the MIIC and abrogates TLR9 activation. Like anergy, this block in endocytic trafficking is rapidly reversible. These findings indicate that cellular responsiveness can be determined by mechanisms that control the subcellular location of important immune recognition receptors.
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DOI：
10.1084/jem.20060221
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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通讯作者：
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发表时间：
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发表时间：
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期刊：
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影响因子：
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发表时间：
1993-04-01
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影响因子：
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发表时间：
2009-08
期刊：
Nature reviews. Immunology
影响因子：
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