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Antibody repertoire and gene expression dynamics of diverse human B cell states during affinity maturation.
bioRxiv - Immunology Pub Date : 2020-05-26 , DOI: 10.1101/2020.04.28.054775
Hamish W King , Nara Orban , John C Riches , Andrew J Clear , Gary Warnes , Sarah A Teichmann , Louisa K James

In response to antigen challenge, B cells clonally expand, undergo selection and differentiate to produce mature B cell subsets and high affinity antibodies. However, the interplay between dynamic B cell states and their antibody-based selection is challenging to decipher in primary human tissue. We have applied an integrated analysis of bulk and single-cell antibody repertoires paired with single-cell transcriptomics of human B cells undergoing affinity maturation. We define unique gene expression and antibody repertoires of known and novel B cell states, including a pre-germinal centre state primed to undergo class switch recombination. We dissect antibody class-dependent gene expression of germinal centre and memory B cells to find that class switching prior to germinal centre entry can have significant implications for the capacity of B cells to undergo antibody-based selection and differentiate. Together, our analyses provide unprecedented resolution into the gene expression and selection dynamics that shape B cell-mediated immunity.

中文翻译:

亲和力成熟过程中各种人类B细胞状态的抗体库和基因表达动态。

响应抗原攻击,B细胞克隆扩增,经历选择和分化,以产生成熟的B细胞亚群和高亲和力抗体。但是,动态B细胞状态与其基于抗体的选择之间的相互作用对于解密人类原始组织具有挑战性。我们已对经历亲和力成熟的人类B细胞的单细胞转录组学与配对的大容量和单细胞抗体库进行了综合分析。我们定义了已知和新颖的B细胞状态的独特基因表达和抗体库,其中包括引发了类转换重组的发芽前中心状态。我们剖析了生发中心和记忆B细胞的抗体类依赖性基因表达,发现生发中心进入之前的类切换可能会对B细胞进行基于抗体的选择和分化的能力产生重大影响。总之,我们的分析为塑造B细胞介导的免疫力的基因表达和选择动力学提供了前所未有的解决方案。
更新日期:2020-05-26
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