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Humoral immunity, the underestimated player in hepatitis B

Cellular & Molecular Immunology volume 15, pages 645–648 (2018)Cite this article

Over decades, the immunological research of hepatitis B virus (HBV) infection has focused on HBV-specific T cells. In chimpanzees acutely infected with HBV, the deletion of CD4+ or CD8+ T cells causes chronic HBV infection. In humans, the HBV-specific T-cell response is temporally correlated with serum HBV clearance during an acute HBV infection, whereas HBV-specific T cells are both quantitatively and qualitatively defective in chronic HBV patients. These studies have suggested that the viral clearance predominately depends on the vigor and specificity of the T-cell responses, which are well summarized by a previous review.1 In contrast, humoral immunity, including B cells and anti-HBV antibody, which may also stop HBV infections, has largely been neglected. However, clinical practices have recently identified the potential importance of B-cell-mediated humoral immunity in the clearance or suppression of HBV infection. Emerging evidence has highlighted B-cell immune features2 and antibody-based prognosis3 and therapy4 in chronic HBV infection. However, many questions remain that prevent a clear understanding of the roles of humoral immunity and its protective mechanisms, which hold the key for their ultimate applications in curing chronic hepatitis B (CHB).

In general, by secreting neutralizing antibodies, B cells can limit viral infection and significantly contribute to viral elimination. Clinical practices have repeatedly shown that B-cell depletion with rituximab against CD20 was the riskiest factor for HBV reactivation among different immune-suppressive agents in lymphoma patients with previously controlled HBV;5 thus these findings indicate that an antibody to HBV is essential to maintain HBV under immune surveillance. An unexpected hepatitis B surface antigen (HBsAg) clearance has also been frequently encountered after bone marrow transplantation from vaccinated donors to CHB recipients.6 For HBV-infected patients receiving liver transplantation, the adoptive anti-HBV immunity (likely both cellular and humoral immunity) from donors potentially clears the residual virus and protects the liver graft from HBV reinfection.7 Moreover, anti-HBsAg antibodies (HBsAb) recognize circulating HBsAg and clear infectious HBV particles in vivo, and the presence of HBsAb in serum is considered an indicator of the resolution of CHB. These data suggest that B-cell-based humoral immunity may act as a key element for long-term HBV control.

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Acknowledgements

We thank Professor Yang-Xin Fu for his critical review of the manuscript. This study was supported, in part, by grants from the National Science Fund for Outstanding Young Scholars (81222024 to ZZ).

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  1. Shanghai Public Health Clinical Center and Institute of Biomedical Sciences, Fudan University, 201508, Shanghai, China

    Shuye Zhang

  2. Research Center for Clinical & Translational Medicine, Beijing 302 Hospital, 100039, Beijing, China

    Juanjuan Zhao & Zheng Zhang

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Correspondence to Zheng Zhang.

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Zhang, S., Zhao, J. & Zhang, Z. Humoral immunity, the underestimated player in hepatitis B. Cell Mol Immunol 15, 645–648 (2018). https://doi.org/10.1038/cmi.2017.132

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