Greiff Victor, Menzel Ulrike, Miho Enkelejda, Weber Cédric, Riedel René, Cook Skylar, Valai Atijeh, Lopes Telma, Radbruch Andreas, Winkler Thomas H, Reddy Sai T
Department of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
German Rheumatism Research Center, a Leibniz Institute, Berlin 10117, Germany.
Cell Rep. 2017 May 16;19(7):1467-1478. doi: 10.1016/j.celrep.2017.04.054.
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.
抗体库的多样性和可塑性对于广泛的保护性免疫至关重要。在多个B细胞发育阶段以及对抗原暴露的反应中，抗体库在大小和多样性方面都会发生变化。然而，我们仍然缺乏对抗体库多样性预先确定程度的基本定量理解。因此，我们实施了一个系统免疫学框架，在三个不同层面上量化抗体库的预先确定：（1）B细胞发育（前B细胞、初始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（4亿条读数）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、抗体库大小）。在所有三个层面上，我们都检测到了高度遗传因素（例如，初始B细胞中V基因使用和克隆扩增的比例>90%）和抗原驱动因素（例如，浆细胞中克隆多样性的比例为40%）预先确定与随机变化之间的动态平衡。我们的研究对体液免疫的预测和调控具有启示意义。
