Humoral immunity in hepatitis B virus infection: Rehabilitating the B in HBV

JHEP Rep. 2021 Nov 19;4(2):100398. doi: 10.1016/j.jhepr.2021.100398. eCollection 2022 Feb.

Abstract

Insights into the immunopathogenesis of chronic HBV infections are fundamental in the quest for novel treatment approaches aimed at a functional cure. While much is known about the ineffective HBV-specific T-cell responses that characterise persistent HBV replication, B cells have been left largely understudied. However, an important role for humoral immunity during the natural history of HBV infections, as well as after functional cure, has been inadvertently revealed by the occurrence of HBV flares following B cell-depleting treatments. Herein, we review our current understanding of the role of the humoral immune response in chronic HBV, both at the level of HBV-specific antibody production and at the phenotypic and broader functional level of B cells. The recent development of fluorescently labelled HBV proteins has given us unprecedented insights into the phenotype and function of HBsAg- and HBcAg-specific B cells. This should fuel novel research into the mechanisms behind dysfunctional HBsAg-specific and fluctuating, possibly pathogenic, HBcAg-specific B-cell responses in chronic HBV. Finally, novel immunomodulatory treatments that partly target B cells are currently in clinical development, but a detailed assessment of their impact on HBV-specific B-cell responses is lacking. We plead for a rehabilitation of B-cell studies related to both the natural history of HBV and treatment development programmes.

Keywords: ADCC, antibody-dependent cellular cytotoxicity; ALT, alanine aminotransferase; AtMBCs, atypical memory B cells; B cells; CHB, chronic hepatitis B; DEGs, differentially expressed genes; ENEG, HBeAg-negative chronic hepatitis; Fcrl5, Fc receptor-like 5; HBV-ALF, HBV-induced acute liver failure; HBcAb, hepatitis B core antibodies; HBcrAg, hepatitis B core-related antigen; HBsAb, hepatitis B surface antibodies; HC, healthy controls; HbeAb, hepatitis B e antibodies; IL-, interleukin-; MBC, memory B cells; NA s, nucleos(t)ide analogues; ORF, open reading frame; PBMC, peripheral blood mononuclear cells; PD-1, programmed cell death 1; TLR, Toll-like receptor; antibodies; cccDNA, covalently closed circular DNA; flares; global B cells; hepatitis B virus; hepatitis B-specific B cells; iMATE, intrahepatic myeloid-cell aggregates.

Publication types

  • Review