BACKGROUND Studies on chronic hepatitis B virus (HBV) infection have shown immune dysfunction involving multiple cell types, including T cells. B cells have been evaluated more recently, but in contrast to T cells, more pronounced activation of circulating B cells has been reported. To gain more insight into the activation status of B cells, we investigated gene profiles of B cells in the blood and liver of patients with chronic HBV. METHODS RNA-sequencing and flow cytometric analysis was performed on peripheral blood B cells of patients with immune active chronic HBV, comparing them with samples from healthy controls. In addition, gene expression profiles of B cells in the liver were analyzed by bulk and single-cell RNA-seq. RESULTS Our data show a distinctive B-cell activation gene signature in the blood of patients with immune active chronic HBV, characterized by a significant upregulation of immune-related genes. This peripheral activation profile was also observed in B cells from the liver by single-cell RNA-seq, with naive and memory B-cell subsets being the primary carriers of the signature. CONCLUSIONS Our findings suggest that B-cell gene profiles reflect responsiveness to HBV infection; these findings are relevant for clinical studies evaluating immunomodulatory treatment strategies for HBV.

中文翻译：

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乙型肝炎 e 抗原阳性免疫活动性慢性乙型肝炎患者血液和肝脏中的 B 细胞活化基因特征。


背景 对慢性乙型肝炎病毒 （HBV） 感染的研究表明，免疫功能障碍涉及多种细胞类型，包括 T 细胞。B 细胞最近进行了更严格的评估，但与 T 细胞相比，已报道循环 B 细胞的激活更明显。为了更深入地了解 B 细胞的激活状态，我们研究了慢性 HBV 患者血液和肝脏中 B 细胞的基因谱。方法 对免疫活动性慢性 HBV 患者的外周血 B 细胞进行 RNA 测序和流式细胞术分析，并将其与健康对照的样本进行比较。此外，通过大量和单细胞 RNA-seq 分析肝脏中 B 细胞的基因表达谱。结果我们的数据显示，免疫活动性慢性 HBV 患者血液中存在独特的 B 细胞活化基因特征，其特征是免疫相关基因的显着上调。通过单细胞 RNA-seq 在肝脏的 B 细胞中也观察到这种外周激活谱，其中幼稚和记忆 B 细胞亚群是特征的主要载体。结论 我们的研究结果表明，B 细胞基因谱反映了对 HBV 感染的反应性;这些发现与评估 HBV 免疫调节治疗策略的临床研究相关。