The full diversity of the circulating human B cell compartment is unknown. Flow cytometry analysis suggests that in addition to naive and memory B cells, there exists a population of CD11c+, CD27- CD21- atypical B cells, that are associated with chronic or recurrent infection and autoimmunity. We used single cell RNA-seq approaches to examine the diversity of both antigen-specific B cells and total B cells in healthy subjects and individuals naturally-exposed to recurrent malaria infections. This analysis revealed two B cell lineages: a classical lineage of activated and resting memory B cells, and an atypical-like lineage. Surprisingly, the atypical lineage was common in both malaria exposed individuals and non-exposed healthy controls. Using barcoded antibodies in conjunction with our transcriptomic data, we found that atypical lineage cells in healthy individuals lack many atypical B markers and thus represent an undercounted cryptic population. We further determined using antigen specific probes that atypical cells can be induced by primary vaccination in humans and can be recalled upon boosting. Collectively these data suggest that atypical cells are not necessarily pathogenic but can be a normal component of B responses to antigen.

中文翻译：

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非典型B细胞是人类对疫苗接种和感染的免疫反应的正常组成部分

循环中的人类B细胞区室的完全多样性是未知的。流式细胞仪分析表明，除幼稚和记忆B细胞外，还有一群CD11c +，CD27- CD21-非典型B细胞，它们与慢性或复发性感染和自身免疫性有关。我们使用单细胞RNA-seq方法检查健康受试者和自然暴露于复发性疟疾感染的个体中抗原特异性B细胞和总B细胞的多样性。该分析揭示了两个B细胞谱系：活化和静止记忆B细胞的经典谱系，以及非典型样谱系。令人惊讶的是，非典型谱系在疟疾接触者和未接触健康对照者中都很常见。结合条形码抗体和我们的转录组数据，我们发现健康个体中的非典型谱系细胞缺乏许多非典型B标记，因此代表了被低估的隐性种群。我们进一步使用抗原特异性探针确定非典型细胞可以通过人初次接种疫苗诱导，并且可以在加强免疫后召回。总的来说，这些数据表明非典型细胞不一定是致病的，但可以是B对抗原反应的正常组成部分。