Anergy in self-directed B lymphocytes: A statistical mechanics perspective
Anergy in self-directed B lymphocytes: A statistical mechanics perspective
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DOI：
10.1016/j.jtbi.2014.05.006
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发表时间：
2015-06-21
影响因子：
2
通讯作者：
Tantari, Daniele
中科院分区：
文献类型：
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作者：
Agliari, Elena;Barra, Adrian;Tantari, Daniele
自我导向的淋巴细胞在个体发生时可能会逃避克隆缺失，但由于一种称为克隆无反应性的机制，仍然保持无害。对于B淋巴细胞，在过去几十年中发展了两种主要的无反应性解释：根据瓦雷拉理论，无反应性源于整个B细胞库的适当编排，例如自我反应克隆，由于来自其他克隆的强烈反馈，在建立反应时表现出强烈的惰性。相反，根据同源反应的模型，自我反应细胞不受辅助淋巴细胞的刺激，并且这种信号传导的缺乏产生无反应性。通过统计力学，我们发现，辅助细胞并不能激活B细胞的一个亚群：值得注意的是，后者只是那些在独特型网络中广泛相互作用的细胞。因此，瓦雷拉理论最终可以被重新吸收到同源反应模型的主流框架中。此外，我们展示了如何B-剧目架构可能会出现，高度连接的克隆自我导向的个体发育学习的自然结果。(C)2014爱思唯尔有限公司版权所有。
Self-directed lymphocytes may evade clonal deletion at ontogenesis but still remain harmless due to a mechanism called clonal anergy. For B-lymphocytes, two major explanations for anergy developed over the last decades: according to Varela theory, anergy stems from a proper orchestration of the whole B-repertoire, such that self-reactive clones, due to intensive feed-back from other clones, display strong inertia when mounting a response. Conversely, according to the model of cognate response, self-reacting cells are not stimulated by helper lymphocytes and the absence of such signaling yields anergy. Through statistical mechanics we show that helpers do not prompt activation of a sub-group of B-cells: remarkably, the latter are just those broadly interacting in the idiotypic network. Hence Varela theory can finally be reabsorbed into the prevailing framework of the cognate response model. Further, we show how the B-repertoire architecture may emerge, where highly connected clones are self-directed as a natural consequence of ontogenetic learning. (C) 2014 Elsevier Ltd. All rights reserved.