title: Reversal of B-cell hyperactivation and functional impairment is associated with HBsAg seroconversion in chronic hepatitis B patients.
abstract: B cells play an important role in the clearance of hepatitis B virus (HBV) and protection against reinfection. However, the functional characteristics of these cells that are associated with the outcome of chronic HBV infection remain unknown. We comprehensively investigated the frequency, phenotype, and function of peripheral B-cell subsets from CHB patients in different phases: immune tolerance (IT), immune activation (IA), immune clearance (IC), responders with HBsAg seroconversion (resolved patients, RP), and healthy controls (HC). IA patients displayed lower percentages of peripheral blood memory B cells compared with the other groups. Overall polyclonal activation of B cells, indicated by higher levels of activation markers and secretion of IgG and IgM, was observed in IA patients. This B-cell hyperactivation could be induced by increased IFN-α and soluble CD40 ligands in IA patients. Notably, the expression of the co-stimulator molecule CD80 and serum HBsAb and the frequency of HBsAg-specific B cells were significantly decreased in IT, IA, and IC patients compared with HC subjects. More importantly, the B-cell hyperactivation, co-stimulatory molecule downregulation and HBsAg-specific B-cell impairment were reversed in RP patients. The reversal of B-cell hyperactivation and functional impairment is associated with HBsAg seroconversion in chronic hepatitis B patients.
authors: 1] Beijing Institute of Radiation Medicine, Beijing, China [2] Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing 100039, China.
authors: Xiangsheng
authors: X
authors: Xu
authors: Department of Infectious Diseases, 88th Hospital of PLA, Taian, Shandong, China.
authors: Qinghua
authors: Q
authors: Shang
authors: Department of Infectious Diseases, Beijing You'an Hospital, Affiliated to Capital Medical University, Beijing, China.
authors: Xinyue
authors: X
authors: Chen
authors: Department of Infectious Diseases, Beijing 302 Hospital, Beijing, China.
authors: Weimin
authors: W
authors: Nie
authors: Department of Non-infectious Diseases, Beijing 302 Hospital, Beijing, China.
authors: Zhengsheng
authors: Z
authors: Zou
authors: Department of Non-infectious Diseases, Beijing 302 Hospital, Beijing, China.
authors: Ang
authors: A
authors: Huang
authors: Institute of Basic Medicine, Hebei University, Baoding, China.
authors: Ming
authors: M
authors: Meng
authors: Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing 100039, China.
authors: Lei
authors: L
authors: Jin
authors: Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing 100039, China.
authors: Ruonan
authors: R
authors: Xu
authors: Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing 100039, China.
authors: Ji-Yuan
authors: JY
authors: Zhang
authors: Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing 100039, China.
authors: Junliang
authors: J
authors: Fu
authors: Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing 100039, China.
authors: Lifeng
authors: L
authors: Wang
authors: Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing 100039, China.
authors: Zirong
authors: Z
authors: Tang
authors: Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing 100039, China.
authors: Yunbo
authors: Y
authors: Xie
authors: Beijing Institute of Radiation Medicine, Beijing, China.
authors: Xiaoming
authors: X
authors: Yang
authors: Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing 100039, China.
authors: Zheng
authors: Z
authors: Zhang
authors: Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing 100039, China.
authors: Fu-Sheng
authors: FS
authors: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007156:Immunologic Memory; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D000069078:Seroconversion; D019562:Viral Load; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D018122:B7-1 Antigen; D019013:CD40 Antigens; D016898:Interferon-alpha