Circulating HBsAg-specific B cells are partially rescued in chronically HBV-infected patients with functional cure

作者：Shuqin Gu, Libo Tang, Ling Guo, Chun-Xiu Zhong, Xin Fu, Guofu Ye, Shihong Zhong, Xiaoyi Li, Chunhua Wen, Yang Zhou, Jinling Wei, Haitao Chen, Nikolai Novikov, Simon P. Fletcher, M. Anthony Moody, Jinlin Hou, Yongyin Li · 发表于：Emerging Microbes & Infections · 年份：2024 · DOI：10.1080/22221751.2024.2409350 · 被引用次数：8 · 研究领域：Hepatitis B Virus Studies、Hepatitis C virus research、Liver Disease Diagnosis and Treatment

It is well established that humoral immunity targeting hepatitis B virus surface antigen (HBsAg) plays a critical role in viral clearance and clinical cure. However, the functional changes in HBsAg-specific B cells before and after achieving functional cure remain poorly understood. In this study, we characterized circulating HBsAg-specific B cells and identified functional shifts and B-cell epitopes directly associated with HBsAg loss. The phenotypes and functions of HBV-specific B cells in patients with chronic HBV infection were investigated using a dual staining method and the ELISpot assay. Epitope mapping was performed to identify B cell epitopes associated with functional cure. Hyperactivated HBsAg-specific B cells in patients who achieved HBsAg loss were composed of enriched resting memory and contracted atypical memory fractions, accompanied by sustained co-expression of multiple inhibitory receptors and increased IL-6 secretion. The frequency of HBsAb-secreting B cells was significantly increased after achieving a functional cure. The rHBsAg displayed a weaker immunomodulatory effect on B cells than rHBeAg and rHBcAg in vitro. Notably, sera from patients with HBsAg loss reacted mainly with peptides S60, S61, and S76, suggesting that these are dominant linear B-cell epitopes relevant for functional cure. Intriguingly, patients reactive with S76 showed a higher frequency of the HLA class II DQB1*05:01 allele. Taken together, HBsAg-specific B cells were partially resto...