An Integrated Multi-omic Single-Cell Atlas of Human B Cell Identity

An Integrated Multi-omic Single-Cell Atlas of Human B Cell Identity
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DOI:
10.1016/j.immuni.2020.06.013
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发表时间:
2020-07-14
期刊:
影响因子:
32.4
通讯作者:
Bendall, Sean C.
Bendall, Sean C.
中科院分区:
医学1区
文献类型:
--
作者:
Glass, David R.;Tsai, Albert G.;Bendall, Sean C.

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B细胞具有广泛的效应功能,包括抗体分泌、抗原递呈、细胞因子的产生和免疫记忆的产生。使用表面分子对人类B细胞进行分类的一致策略对于利用这种功能多样性进行临床翻译至关重要。我们开发了一种高度多重的屏幕来量化数百万人B细胞上351个表面分子的共表达。我们鉴定了差异表达的分子,并将它们的变化与同型使用、VDJ序列、代谢谱、生物合成活性和信号响应进行了比对。基于这些分析,我们提出了一个分类方案,将来自四个淋巴组织的B细胞分为12个独特的亚群,包括CD45RB(+)CD27(-)早期记忆群,类切换CD39(+)驻留扁桃体的人群,以及对免疫激活有潜在反应的CD19(HI)CD11(+)记忆群。这一分类框架和基础数据集为进一步研究人类B细胞的特性和功能提供了资源。
B cells are capable of a wide range of effector functions including antibody secretion, antigen presentation, cytokine production, and generation of immunological memory. A consistent strategy for classifying human B cells by using surface molecules is essential to harness this functional diversity for clinical translation. We developed a highly multiplexed screen to quantify the co-expression of 351 surface molecules on millions of human B cells. We identified differentially expressed molecules and aligned their variance with isotype usage, VDJ sequence, metabolic profile, biosynthesis activity, and signaling response. Based on these analyses, we propose a classification scheme to segregate B cells from four lymphoid tissues into twelve unique subsets, including a CD45RB(+)CD27(-) early memory population, a class-switched CD39(+) tonsil-resident population, and a CD19(hi)CD11(+) memory population that potently responds to immune activation. This classification framework and underlying datasets provide a resource for further investigations of human B cell identity and function.