B Cell-mediated Humoral Immunity in Chronic Hepatitis B Infection - PubMed (original) (raw)

Review

. 2021 Aug 28;9(4):592-597.

doi: 10.14218/JCTH.2021.00051. Epub 2021 May 27.

Shengxia Yin 2, Rahma Issa 3, Xin Tong 2, Guiyang Wang 2, Juan Xia 2, Rui Huang 2, Guangmei Chen 4, Dan Weng 1, Chen Chen 5, Chao Wu 2, Yuxin Chen 6

Affiliations

Review

B Cell-mediated Humoral Immunity in Chronic Hepatitis B Infection

Yang Li et al. J Clin Transl Hepatol. 2021.

Abstract

B cell-mediated humoral immunity plays a vital role in viral infections, including chronic hepatitis B virus (HBV) infection, which remains a critical global public health issue. Despite hepatitis B surface antigen-specific antibodies are essential to eliminate viral infections, the reduced immune functional capacity of B cells was identified, which was also correlated with chronic hepatitis B (CHB) progression. In addition to B cells, T follicular helper (Tfh) cells, which assist B cells to produce antibodies, might also be involved in the process of anti-HBV-specific antibody production. Here, we provide a comprehensive review of the role of various subsets of B cells and Tfh cells during CHB progression and discuss current novel treatment strategies aimed at restoring humoral immunity. Understanding the mechanism of dysregulated B cells and Tfh cells will facilitate the ultimate functional cure of CHB patients.

Keywords: Antibody; B cell; Chronic hepatitis B (CHB); T follicular helper (Tfh) cells; Therapeutics.

© 2021 Authors.

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Conflict of interest statement

The authors have no conflict of interests related to this publication.

Figures

Fig. 1

Fig. 1. B cell-mediated humoral immunity in immunized healthy individuals and CHB patients.

(A) HBsAb production by HBsAg-specific B cells in immunized healthy individuals plays a pivotal role in the clearance of HBV. A major antiviral role for HBsAb is viral clearance, mediated by neutralization, antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Tfh cells could assist B cell function by expressing cytokines such as IL-21, IL-6 and IL-4 and direct interactions through CD40L/CD40. (B) In CHB patients, B cells were phenotypically dysfunctional with increased expression of T-bet, TLR7/9 and FcRL5. During CHB infection, despite HBcAg-specific B cells being class-switched memory B cells and secrete anti-HBc, HBsAg-specific B cells fail to mature efficiently into antibody secreting cells, leading to the scarcity of serological anti-HBs. Beyond the traditional role of antibody production, HBV-specific B cells might efficiently serve as a primary source of APC for T cells and induce CTLs responses. Moreover, B cells can produce cytokines such as IL-10 to inhibit the function of effector T cells and enhance Treg cell function. TFR and Treg cells can impair the Tfh function by secreting IL-10 and expressing CTLA4. The dysregulated B cells, Tfh cells, TFR cells and Treg cells might contribute to the defective function of B cell mediated humoral immunity during CHB infection. HBV, hepatitis B virus; CHB, chronic hepatitis B; Tfh, T follicular helper; HBsAg, hepatitis B surface antigen; APCs, antigen-presenting cells; TLR, toll-like receptor; IL-10, interleukin-10.

References

    1. Hepatitis B virus infection. Nat Rev Dis Primers. 2018;4:18036. doi: 10.1038/nrdp.2018.36. - DOI - PubMed
    1. Chu CM, Liaw YF. Hepatitis B surface antigen seroclearance during chronic HBV infection. Antivir Ther. 2010;15(2):133–143. doi: 10.3851/IMP1497. - DOI - PubMed
    1. Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008;48(2):335–352. doi: 10.1016/j.jhep.2007.11.011. - DOI - PubMed
    1. Konerman MA, Lok AS. Interferon treatment for hepatitis B. Clin Liver Dis. 2016;20(4):645–665. doi: 10.1016/j.cld.2016.06.002. - DOI - PubMed
    1. Lazarus JV, Sperle I, Safreed-Harmon K, Gore C, Cebolla B, Spina A. Associations between national viral hepatitis policies/programmes and country-level socioeconomic factors: a sub-analysis of data from the 2013 WHO viral hepatitis policy report. BMC Public Health. 2017;18(1):16. doi: 10.1186/s12889-017-4549-4. - DOI - PMC - PubMed

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