BCR寡聚体的形成提供了B细胞亲和力识别的机制
Formation of BCR Oligomers Provides a Mechanism for B cell Affinity Discrimination
摘要：
B细胞在很宽的亲和力范围内遇到抗原。响应于抗原的B细胞信号转导的强度随着亲和力而增加，该过程称为“亲和力辨别”。在这项工作中，我们使用的B细胞表面动力学和信号的计算机模拟表明，亲和歧视可以从BCR寡聚体的形成。已知BCR在遇到抗原时形成寡聚体，并且这些寡聚体的大小和形成速率随着亲和力而增加。在我们的模拟中，我们引入了一个要求，即只有BCR-抗原复合物是寡聚体的一部分，才能参与细胞质信号分子，如Src家族激酶。我们的模拟表明，随着亲和力的增加，不仅收集的抗原数量增加，信号传导活性也增加。我们的结果也与实验观察到的激活阈值亲和力（低于该亲和力值没有信号传导活性）和亲和力辨别上限（高于该亲和力值没有亲和力辨别）的存在一致。与实验的比较表明，我们的模型预测的二聚体形成的时间尺度（小于10秒）是很好的实验观察到的关联BCR与Src家族激酶（10-20秒）的时间尺度内。
英文摘要：
B cells encounter antigen over a wide affinity range. The strength of B cell signaling in response to antigen increases with affinity, a process known as "affinity discrimination". In this work, we use a computational simulation of B cell surface dynamics and signaling to show that affinity discrimination can arise from the formation of BCR oligomers. It is known that BCRs form oligomers upon encountering antigen, and that the size and rate of formation of these oligomers increase with affinity. In our simulation, we have introduced a requirement that only BCR-antigen complexes that are part of an oligomer can engage cytoplasmic signaling molecules such as Src-family kinases. Our simulation shows that as affinity increases, not only does the number of collected antigen increases, but so does signaling activity. Our results are also consistent with the existence of an experimentally-observed threshold affinity of activation (no signaling activity below this affinity value) and affinity discrimination ceiling (no affinity discrimination above this affinity value). Comparison with experiments shows that the time scale of dimer formation predicted by our model (less than 10 s) is well within the time scale of experimentally observed association of BCR with Src-family kinases (10-20 s).
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