Several infectious and autoimmune diseases are associated with an expansion of CD21 − CD27 − atypical B cells (atBCs) that up-regulate inhibitory receptors and exhibit altered B cell receptor (BCR) signaling. The function of atBCs remains unclear, and few studies have investigated the biology of pathogen-specific atBCs during acute infection. Here, we performed longitudinal flow cytometry analyses and RNA sequencing of Plasmodium falciparum ( Pf )–specific B cells isolated from study participants before and shortly after febrile malaria, with simultaneous analysis of influenza hemagglutinin (HA)–specific B cells as a comparator. At the healthy baseline before the malaria season, individuals had similar frequencies of Pf - and HA-specific atBCs that did not differ proportionally from atBCs within the total B cell population. BCR sequencing identified clonal relationships between Pf -specific atBCs, activated B cells (actBCs), and classical memory B cells (MBCs) and revealed comparable degrees of somatic hypermutation. At the healthy baseline, Pf -specific atBCs were transcriptionally distinct from Pf -specific actBCs and classical MBCs. In response to acute febrile malaria, Pf -specific atBCs and actBCs up-regulated similar intracellular signaling cascades. Pf -specific atBCs showed activation of pathways involved in differentiation into antibody-secreting cells and up-regulation of molecules that mediate B-T cell interactions, suggesting that atBCs respond to T follicular helper (T FH ) cells. In the presence of T FH cells and staphylococcal enterotoxin B, atBCs of malaria-exposed individuals differentiated into CD38 + antibody-secreting cells in vitro, suggesting that atBCs may actively contribute to humoral immunity to infectious pathogens.

中文翻译：

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非典型 B 细胞在疟疾期间上调共刺激分子并在滤泡辅助 T 细胞支持下分泌抗体


多种传染性和自身免疫性疾病与 CD21 的扩增有关- CD27 -非典型 B 细胞 (atBC) 上调抑制性受体并表现出改变的 B 细胞受体 (BCR) 信号传导。 atBC 的功能仍不清楚，很少有研究调查急性感染期间病原体特异性 atBC 的生物学。在这里，我们进行了纵向流式细胞术分析和 RNA 测序恶性疟原虫（普夫）——从研究参与者患热性疟疾之前和之后不久分离出的特异性 B 细胞，同时分析流感血凝素 (HA)——特异性 B 细胞作为比较。在疟疾季节之前的健康基线上，个体的疟疾发生频率相似普夫- 和 HA 特异性 atBC，与总 B 细胞群中的 atBC 没有成比例的差异。 BCR 测序鉴定了之间的克隆关系普夫-特异性 atBC、活化 B 细胞 (actBC) 和经典记忆 B 细胞 (MBC)，并揭示了相当程度的体细胞超突变。在健康基线下，普夫-特定的 atBC 在转录上不同于普夫-特定的 actBC 和经典 MBC。为了应对急性发热性疟疾，普夫-特定的 atBC 和 actBC 上调类似的细胞内信号级联。普夫- 特异性 atBC 显示参与分化为抗体分泌细胞的途径的激活以及介导 BT 细胞相互作用的分子的上调，表明 atBC 对 T 滤泡辅助细胞 (T跳频）细胞。 在 T 存在的情况下跳频疟疾暴露个体的细胞和葡萄球菌肠毒素 B、atBC 分化为 CD38 +体外抗体分泌细胞，表明 atBC 可能积极促进针对传染性病原体的体液免疫。