Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of Antibody Repertoires throughout B Cell Development
Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of Antibody Repertoires throughout B Cell Development
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DOI：
10.1016/j.celrep.2017.04.054
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发表时间：
2017-05-16
期刊：
影响因子：
8.8
通讯作者：
Reddy, Sai T.
中科院分区：
文献类型：
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作者：
Greiff, Victor;Menzel, Ulrike;Reddy, Sai T.
抗体库的多样性和可塑性是广泛保护性免疫的关键。在多个B细胞发育阶段和抗原暴露的反应中，谱的大小和多样性会发生变化。然而，我们仍然缺乏基本的定量理解，在多大程度上保留曲目的多样性是预先确定的。因此，我们实施了一个系统免疫学框架，用于在三个不同水平上定量库预确定：(1)B细胞发育（前B细胞，幼稚B细胞，浆细胞），(2)抗原暴露（三种结构不同的蛋白质），以及(3)从抗体库测序数据（4亿reads）中提取的四种抗体库成分（v基因使用，克隆扩增，克隆多样性，库大小）。在所有三个水平上，我们检测到高遗传（例如，在初始B细胞中v基因的使用和克隆扩增为> - 90%）和抗原驱动（例如，在浆细胞中克隆多样性为40%）预先决定和随机变异的动态平衡。我们的研究对体液免疫的预测和操纵具有启示意义。
Antibody repertoire diversity and plasticity is crucial for broad protective immunity. Repertoires change in size and diversity across multiple B cell developmental stages and in response to antigen exposure. However, we still lack fundamental quantitative understanding of the extent to which repertoire diversity is predetermined. Therefore, we implemented a systems immunology framework for quantifying repertoire predetermination on three distinct levels: (1) B cell development (pre-B cell, naive B cell, plasma cell), (2) antigen exposure (three structurally different proteins), and(3) four antibody repertoire components (V-gene usage, clonal expansion, clonal diversity, repertoire size) extracted from antibody repertoire sequencing data (400 million reads). Across all three levels, we detected a dynamic balance of high genetic (e.g., >90% for V-gene usage and clonal expansion in naive B cells) and antigen-driven (e.g., 40% for clonal diversity in plasma cells) predetermination and stochastic variation. Our study has implications for the prediction and manipulation of humoral immunity.