Antibody memory protects humans from many diseases. Protective antibody memory responses require activation of transcriptional programs, cell proliferation, and production of antigen-specific antibodies, but how these aspects of the response are coordinated is poorly understood. We profile the molecular and cellular features of the antibody response to influenza vaccination by integrating single-cell transcriptomics, longitudinal antibody repertoire sequencing, and antibody binding measurements. Single-cell transcriptional profiling reveals a program of memory B cell activation characterized by CD11c and T-bet expression associated with clonal expansion and differentiation toward effector function. Vaccination elicits an antibody clone, which rapidly acquired broad high-affinity hemagglutinin binding during affinity maturation. Unexpectedly, many antibody clones elicited by vaccination do not bind vaccine, demonstrating non-specific activation of bystander antibodies by influenza vaccination. These results offer insight into how molecular recognition, transcriptional programs, and clonal proliferation are coordinated in the human B cell repertoire during memory recall.

中文翻译：

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单细胞转录组学揭示了记忆B细胞激活，广泛的抗流感抗体和旁观者激活。

抗体记忆可保护人类免受多种疾病的侵害。保护性抗体记忆反应需要转录程序的激活，细胞增殖和抗原特异性抗体的产生，但是如何协调反应的这些方面却知之甚少。通过整合单细胞转录组学，纵向抗体库测序和抗体结合测量，我们分析了流感疫苗接种抗体反应的分子和细胞特征。单细胞转录谱揭示了记忆B细胞活化的程序，其特征在于CD11c和T-bet表达与克隆扩增和向效应子功能的分化有关。疫苗接种会引发抗体克隆，该抗体克隆会在亲和力成熟过程中迅速获得广泛的高亲和力血凝素结合。不料，疫苗接种引发的许多抗体克隆均不结合疫苗，这表明流感疫苗对旁观者抗体的非特异性激活。这些结果提供了在记忆召回过程中如何在人类B细胞谱系中协调分子识别，转录程序和克隆增殖的见解。