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Reversal of B-cell hyperactivation and functional impairment is associated with HBsAg seroconversion in chronic hepatitis B patients

Cellular & Molecular Immunology volume 12, pages 309–316 (2015)Cite this article

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.

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Acknowledgements

This work was supported by grants from the National Grand Program on Key Infectious Disease (2013ZX10002001-001-003, 2012ZX10002-007-002), the National Natural Science Foundation of China (81373137), the National Key Basic Research Program of China (2012CB519005), and the National Science Fund for Outstanding Young Scholars (81222024).

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Author notes

  1. Xiangsheng Xu and Qinghua Shang: Xiangsheng Xu and Qinghua Shang have contributed equally to this work.

  2. Zheng Zhang, Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing 100039, China. E-mail: zhangzheng1975@aliyun.com

  3. Fu-Sheng Wang, Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing 100039, China. E-mail: fswang302@163.com

Authors and Affiliations

  1. Beijing Institute of Radiation Medicine, Beijing, China

    Xiangsheng Xu & Xiaoming Yang

  2. Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, 100039, China

    Xiangsheng Xu, Lei Jin, Ruonan Xu, Ji-Yuan Zhang, Junliang Fu, Lifeng Wang, Zirong Tang, Yunbo Xie, Zheng Zhang & Fu-Sheng Wang

  3. Department of Infectious Diseases, 88th Hospital of PLA, Taian, Shandong, China

    Qinghua Shang

  4. Department of Infectious Diseases, Beijing You'an Hospital, Affiliated to Capital Medical University, Beijing, China

    Xinyue Chen

  5. Department of Infectious Diseases, Beijing 302 Hospital, Beijing, China

    Weimin Nie

  6. Department of Non-infectious Diseases, Beijing 302 Hospital, Beijing, China

    Zhengsheng Zou & Ang Huang

  7. Institute of Basic Medicine, Hebei University, Baoding, China

    Ming Meng

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Xu, X., Shang, Q., Chen, X. et al. Reversal of B-cell hyperactivation and functional impairment is associated with HBsAg seroconversion in chronic hepatitis B patients. Cell Mol Immunol 12, 309–316 (2015). https://doi.org/10.1038/cmi.2015.25

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