High-resolution antibody dynamics of vaccine-induced immune responses
High-resolution antibody dynamics of vaccine-induced immune responses
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DOI：
10.1073/pnas.1323862111
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发表时间：
2014-04-01
影响因子：
11.1
通讯作者：
Church, George M.
中科院分区：
文献类型：
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作者：
Laserson, Uri;Vigneault, Francois;Church, George M.
适应性免疫系统通过产生多种抗体受体库来提供保护，所述抗体受体库响应于特定靶标而快速扩增和收缩。下一代DNA测序现在提供了调查这一复杂而庞大的剧目的机会。在目前的工作中，我们描述了一套工具，用于分析抗体库及其应用，以阐明人类志愿者对病毒疫苗接种的反应动力学。通过分析来自38个独立的血液样本的数据，我们发现，随着时间的推移，V和J片段的种系文库的使用在个体之间是保守的。令人惊讶的是，似乎没有一个特定的VJ组合的使用水平和扩张程度之间的相关性。我们发现每个志愿者的抗体RNA库是高度动态的，每个人都表现出不同的反应动力学。通过使用组合噬菌体展示，我们筛选了与其相应的VL文库配对的所选VH基因，以获得针对疫苗抗原的亲和力。总而言之，这项工作提出了一套额外的工具，用于分析人类抗体库，并证明了在多个个体中响应免疫挑战的快速库动态随时间的表征。
The adaptive immune system confers protection by generating a diverse repertoire of antibody receptors that are rapidly expanded and contracted in response to specific targets. Next-generation DNA sequencing now provides the opportunity to survey this complex and vast repertoire. In the present work, we describe a set of tools for the analysis of antibody repertoires and their application to elucidating the dynamics of the response to viral vaccination in human volunteers. By analyzing data from 38 separate blood samples across 2 y, we found that the use of the germ-line library of V and J segments is conserved between individuals over time. Surprisingly, there appeared to be no correlation between the use level of a particular VJ combination and degree of expansion. We found the antibody RNA repertoire in each volunteer to be highly dynamic, with each individual displaying qualitatively different response dynamics. By using combinatorial phage display, we screened selected VH genes paired with their corresponding VL library for affinity against the vaccine antigens. Altogether, this work presents an additional set of tools for profiling the human antibody repertoire and demonstrates characterization of the fast repertoire dynamics through time in multiple individuals responding to an immune challenge.