乙型肝炎病毒感染的体液免疫：乙型肝炎病毒的康复

StephenW

乙型肝炎病毒感染的体液免疫：乙型肝炎病毒的康复
托马斯·范沃勒格姆 1 2 ，汤姆·阿多马蒂 1 2 ，斯蒂恩·范希斯 1 2 ，哈里·拉·詹森 3
隶属关系
隶属关系

    1
    安特卫普大学医院消化内科和肝病科，比利时安特卫普 2650。
    2
    病毒性肝炎研究小组，实验医学和儿科实验室，安特卫普大学，2650 Antwerp，比利时。
    3
    多伦多肝病中心，大学健康网络，多伦多总医院，多伦多大学，多伦多，ON M5G2C4，加拿大。

    PMID：35059620 PMCID：PMC8760517 DOI：10.1016/j.jhepr.2021.100398

抽象的

深入了解慢性 HBV 感染的免疫发病机制对于寻求针对功能性治愈的新型治疗方法至关重要。虽然人们对作为持续 HBV 复制特征的无效 HBV 特异性 T 细胞反应有很多了解，但 B 细胞在很大程度上还没有得到充分研究。然而，体液免疫在 HBV 感染的自然病程中以及功能性治愈后的重要作用已被 B 细胞耗竭治疗后 HBV 爆发的发生无意中揭示。在这里，我们回顾了我们目前对慢性 HBV 中体液免疫反应作用的理解，包括 HBV 特异性抗体产生水平以及 B 细胞的表型和更广泛的功能水平。最近荧光标记的 HBV 蛋白的发展使我们对 HBsAg 和 HBcAg 特异性 B 细胞的表型和功能有了前所未有的了解。这将推动对慢性 HBV 中功能失调的 HBsAg 特异性和波动的（可能是致病的）HBcAg 特异性 B 细胞反应背后的机制的新研究。最后，部分靶向 B 细胞的新型免疫调节疗法目前正在临床开发中，但缺乏对其对 HBV 特异性 B 细胞反应影响的详细评估。我们呼吁恢复与 HBV 自然史和治疗开发计划相关的 B 细胞研究。

关键词：ADCC，抗体依赖性细胞毒性； ALT，丙氨酸氨基转移酶； AtMBCs，非典型记忆 B 细胞； B细胞； CHB，慢性乙型肝炎； DEGs，差异表达基因； ENEG，HBeAg 阴性慢性肝炎； Fcrl5，Fc受体样5； HBV-ALF，HBV 引起的急性肝功能衰竭； HBcAb，乙型肝炎核心抗体； HBcrAg，乙型肝炎核心相关抗原； HBsAb，乙型肝炎表面抗体； HC，健康对照； HbeAb、乙型肝炎e抗体； IL-，白细胞介素-； MBC，记忆B细胞； NA s，核苷（酸）类似物； ORF，开放阅读框； PBMC，外周血单个核细胞； PD-1，程序性细胞死亡 1； TLR，Toll 样受体；抗体； cccDNA，共价闭合环状 DNA；耀斑;全局 B 细胞；乙型肝炎病毒;乙型肝炎特异性 B 细胞； iMATE，肝内骨髓细胞聚集体。

© 2021 作者。

StephenW

Humoral immunity in hepatitis B virus infection: Rehabilitating the B in HBV
Thomas Vanwolleghem  1   2 , Tom Adomati  1   2 , Stijn Van Hees  1   2 , Harry L A Janssen  3
Affiliations
Affiliations

    1
    Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2650 Antwerp, Belgium.
    2
    Viral Hepatitis Research Group, Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, 2650 Antwerp, Belgium.
    3
    Toronto Centre of Liver Disease, University Health Network, Toronto General Hospital, University of Toronto, Toronto, ON M5G2C4, Canada.

    PMID: 35059620 PMCID: PMC8760517 DOI: 10.1016/j.jhepr.2021.100398

Abstract

Insights into the immunopathogenesis of chronic HBV infections are fundamental in the quest for novel treatment approaches aimed at a functional cure. While much is known about the ineffective HBV-specific T-cell responses that characterise persistent HBV replication, B cells have been left largely understudied. However, an important role for humoral immunity during the natural history of HBV infections, as well as after functional cure, has been inadvertently revealed by the occurrence of HBV flares following B cell-depleting treatments. Herein, we review our current understanding of the role of the humoral immune response in chronic HBV, both at the level of HBV-specific antibody production and at the phenotypic and broader functional level of B cells. The recent development of fluorescently labelled HBV proteins has given us unprecedented insights into the phenotype and function of HBsAg- and HBcAg-specific B cells. This should fuel novel research into the mechanisms behind dysfunctional HBsAg-specific and fluctuating, possibly pathogenic, HBcAg-specific B-cell responses in chronic HBV. Finally, novel immunomodulatory treatments that partly target B cells are currently in clinical development, but a detailed assessment of their impact on HBV-specific B-cell responses is lacking. We plead for a rehabilitation of B-cell studies related to both the natural history of HBV and treatment development programmes.

Keywords: ADCC, antibody-dependent cellular cytotoxicity; ALT, alanine aminotransferase; AtMBCs, atypical memory B cells; B cells; CHB, chronic hepatitis B; DEGs, differentially expressed genes; ENEG, HBeAg-negative chronic hepatitis; Fcrl5, Fc receptor-like 5; HBV-ALF, HBV-induced acute liver failure; HBcAb, hepatitis B core antibodies; HBcrAg, hepatitis B core-related antigen; HBsAb, hepatitis B surface antibodies; HC, healthy controls; HbeAb, hepatitis B e antibodies; IL-, interleukin-; MBC, memory B cells; NA s, nucleos(t)ide analogues; ORF, open reading frame; PBMC, peripheral blood mononuclear cells; PD-1, programmed cell death 1; TLR, Toll-like receptor; antibodies; cccDNA, covalently closed circular DNA; flares; global B cells; hepatitis B virus; hepatitis B-specific B cells; iMATE, intrahepatic myeloid-cell aggregates.

© 2021 The Author(s).

StephenW

http://www.jhep-reports.eu/article/S2589555921001749/pdf