Results from modeling of B-Cell receptors binding to antigen
Results from modeling of B-Cell receptors binding to antigen
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DOI：
10.1016/j.pbiomolbio.2004.01.008
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发表时间：
2004-06-01
影响因子：
3.8
通讯作者：
Bhanot, G
中科院分区：
文献类型：
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作者：
Bhanot, G
80年代末，S、丁齐斯等人提出了自己的观点。进行了一项实验，表明T细胞对B细胞的独立激活需要高价抗原，并且只在很小的抗原浓度范围内发生。这些实验被认为是由“免疫”理论解释的，该理论要求最低数量的受体需要交联才能激活细胞。然而，免疫理论没有考虑受体动力学，不能解释在高抗原浓度或低抗原价时缺乏免疫反应的原因。相反，我们提出了一种简单的新机制，用于T细胞对B细胞的非依赖性激活，其中包括受体内吞作用。我们的模型着重于这样一个事实，对于大多数B细胞在T细胞帮助下被激活的抗原，结合、解结合和吞噬的动力学参数必须被调节，以便在B细胞表面结合的受体数量和内吞的抗原结合受体数量之间存在平衡。这种平衡机制可能是通用的，甚至当B细胞在没有T细胞帮助的情况下被抗原激活时也会发生。通过计算机模拟，我们表明，如果我们接受这一假设，即结合和内吞两种机制之间需要平衡，那么我们可以解释Dintzis实验中的价态截止以及低和高区域耐受性。(C)2004爱思唯尔有限公司。保留所有权利。
In the late 80's, Dintzis et al. conducted an experiment which showed that T-Cell independent activation of B-cells needs high-valence antigen and happens only in a narrow range of antigen concentration. These experiments were believed to be explained by the "immunon" theory that requires that a minimum number of receptors need to be cross-linked to activate a cell. However, the immunon theory does not take into account receptor dynamics and cannot explain the lack of immune response at high antigen concentration or low antigen valence. We propose instead a simple, new mechanism for the T-Cell independent activation of B-Cell, which includes receptor endocytosis. Our model focuses on the fact that for the majority of antigens where the B-Cell is activated with T-Cell help, the kinetic parameters for binding, unbinding and endocytosis must be tuned so that there is an equilibrium between the number of receptors bound on the surface of the B-Cell and the number of antigen-bound receptors endocytosed. This equilibrium mechanism is probably generic and will also occur even when the B-Cell is activated by antigen without T-Cell help. By computer modeling, we show that if we accept this hypothesis of the requirement for equilibrium between the two mechanisms of binding and endocytosis, then we can explain both the valence cutoff and the low and high zone tolerance seen in the Dintzis experiment. (C) 2004 Elsevier Ltd. All rights reserved.