The Diversity and Molecular Evolution of B-Cell Receptors during Infection.
The Diversity and Molecular Evolution of B-Cell Receptors during Infection.
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DOI：
10.1093/molbev/msw015
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发表时间：
2016-05
影响因子：
10.7
通讯作者：
Pybus OG
中科院分区：
文献类型：
--
作者：
Hoehn KB;Fowler A;Lunter G;Pybus OG
B细胞受体（BCR）是识别和结合外源蛋白（抗原）的膜结合免疫球蛋白。BCR是通过生殖系DNA的随机体细胞变化形成的，创造了一个巨大的独特序列库，使个体能够识别各种抗原。在第一次遇到抗原后，BCR经历亲和力成熟的过程，由此快速体细胞突变和选择的循环导致抗原结合的改善。这构成了一个加速的进化过程，需要几天或几周的时间。决定BCR结合的基因区域的下一代测序已经开始以前所未有的细节揭示BCR库的多样性和动态。虽然这种新型的序列数据有可能彻底改变我们对感染动力学的理解，但BCR序列的独特生物学和高度多样性使定量分析变得复杂。已成功应用于快速进化的病原体种群的分子进化和遗传学的模型和概念越来越多地被采用来研究个体内的BCR多样性和分歧。然而，BCR动力学可能违反许多标准进化方法的关键假设，因为它们不是从单一祖先下降，并且经历有偏突变。在这里，我们回顾了进化模型在BCR剧目中的应用，并讨论了我们认为这个跨学科领域蓬勃发展需要解决的问题。
B-cell receptors (BCRs) are membrane-bound immunoglobulins that recognize and bind foreign proteins (antigens). BCRs are formed through random somatic changes of germline DNA, creating a vast repertoire of unique sequences that enable individuals to recognize a diverse range of antigens. After encountering antigen for the first time, BCRs undergo a process of affinity maturation, whereby cycles of rapid somatic mutation and selection lead to improved antigen binding. This constitutes an accelerated evolutionary process that takes place over days or weeks. Next-generation sequencing of the gene regions that determine BCR binding has begun to reveal the diversity and dynamics of BCR repertoires in unprecedented detail. Although this new type of sequence data has the potential to revolutionize our understanding of infection dynamics, quantitative analysis is complicated by the unique biology and high diversity of BCR sequences. Models and concepts from molecular evolution and phylogenetics that have been applied successfully to rapidly evolving pathogen populations are increasingly being adopted to study BCR diversity and divergence within individuals. However, BCR dynamics may violate key assumptions of many standard evolutionary methods, as they do not descend from a single ancestor, and experience biased mutation. Here, we review the application of evolutionary models to BCR repertoires and discuss the issues we believe need be addressed for this interdisciplinary field to flourish.