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Circulating HBsAg-specific B cells are partially rescued in chronically HBV-infected patients with functional cure
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Circulating HBsAg-specific B cells are partially rescued in chronically HBV-infected patients with functional cure
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Journal Article
Circulating HBsAg-specific B cells are partially rescued in chronically HBV-infected patients with functional cure
2024
Overview
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
. 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 restored in patients after achieving a functional cure. Functional cure-related epitopes may be promising targets for developing therapeutic vaccines to treat HBV infection and promote functional cure.
Publisher
Taylor & Francis Ltd,Taylor & Francis,Taylor & Francis Group
Subject
/ B cells
/ Epitopes, B-Lymphocyte - genetics
/ Epitopes, B-Lymphocyte - immunology
/ Female
/ Hepatitis B Antibodies - blood
/ Hepatitis B Antibodies - immunology
/ hepatitis B surface antigen clearance
/ Hepatitis B Surface Antigens - immunology
/ Hepatitis B virus - genetics
/ Hepatitis B virus - immunology
/ Hepatitis B, Chronic - immunology
/ Hepatitis B, Chronic - therapy
/ Hepatitis B, Chronic - virology
/ Hepatitis-Updates from the Classical Emerging Infection
/ Humans
/ Male
