Repertoire comparison of the B-cell receptor-encoding loci in humans and rhesus macaques by next-generation sequencing
Repertoire comparison of the B-cell receptor-encoding loci in humans and rhesus macaques by next-generation sequencing
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DOI：
10.1038/cti.2016.42
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发表时间：
2016-07-01
影响因子：
5.8
通讯作者：
Sather, D. Noah
中科院分区：
文献类型：
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作者：
Vigdorovich, Vladimir;Oliver, Brian G.;Sather, D. Noah
恒河猴（RMs）是一种广泛应用于疫苗、传染病和微生物发病机制研究的模型系统。它们作为模型的价值在于它们与人类的密切进化关系，这在理论上允许它们作为人类免疫系统的近似值。然而，尽管它们作为人类替代模型系统的突出地位，RM免疫系统的许多方面仍然不清楚。特别是，猕猴中B细胞介导的免疫还没有得到充分的表征，B细胞受体编码位点也没有得到充分的注释。为了解决这些空白，我们通过下一代测序分析了人类和rm中循环的重链和轻链谱。通过比较两种植物的V基因片段使用情况、j基因片段使用情况和CDR3长度，我们发现了一些重要的异同点。这些差异在IgM(+) b细胞库中尤为显著。然而，这些转换了类别的、受抗原教育的b细胞群聚集在一组相似的特征上，这意味着每个物种对抗原的反应是相似的。我们的研究首次全面概述了RMs中重链和轻链序列的循环谱，并提供了它们如何作为人类B细胞介导免疫的模型系统的见解。
Rhesus macaques (RMs) are a widely used model system for the study of vaccines, infectious diseases and microbial pathogenesis. Their value as a model lies in their close evolutionary relationship to humans, which, in theory, allows them to serve as a close approximation of the human immune system. However, despite their prominence as a human surrogate model system, many aspects of the RM immune system remain ill characterized. In particular, B cell-mediated immunity in macaques has not been sufficiently characterized, and the B-cell receptor-encoding loci have not been thoroughly annotated. To address these gaps, we analyzed the circulating heavy-and light-chain repertoires in humans and RMs by next-generation sequencing. By comparing V gene segment usage, J-segment usage and CDR3 lengths between the two species, we identified several important similarities and differences. These differences were especially notable in the IgM(+) B-cell repertoire. However, the class-switched, antigen-educated B-cell populations converged on a set of similar characteristics, implying similarities in how each species responds to antigen. Our study provides the first comprehensive overview of the circulating repertoires of the heavy-and light-chain sequences in RMs, and provides insight into how they may perform as a model system for B cell-mediated immunity in humans.