1. Humoral immunity in hepatitis B virus infection: Rehabilitating the B in HBV
- Author
-
Thomas Vanwolleghem, Tom Adomati, Stijn Van Hees, and Harry L.A. Janssen
- Subjects
HBsAg ,Fcrl5, Fc receptor-like 5 ,MBC, memory B cells ,ENEG, HBeAg-negative chronic hepatitis ,Review ,RC799-869 ,medicine.disease_cause ,hepatitis B-specific B cells ,AtMBCs, atypical memory B cells ,HBcAb, hepatitis B core antibodies ,IL-, interleukin ,Immunology and Allergy ,Medicine ,antibodies ,HC, healthy controls ,biology ,Gastroenterology ,virus diseases ,Hepatitis B ,flares ,Diseases of the digestive system. Gastroenterology ,medicine.anatomical_structure ,PBMC, peripheral blood mononuclear cells ,HBeAg ,iMATE, intrahepatic myeloid-cell aggregates ,CHB, chronic hepatitis B ,Antibody ,cccDNA, covalently closed circular DNA ,TLR, Toll-like receptor ,HbeAb, hepatitis B e antibodies ,DEGs, differentially expressed genes ,T cell ,NA s, nucleos(t)ide analogues ,Immune system ,HBcrAg, hepatitis B core-related antigen ,ORF, open reading frame ,ALT, alanine aminotransferase ,HBsAb, hepatitis B surface antibodies ,Internal Medicine ,B cell ,Hepatitis B virus ,B cells ,ADCC, antibody-dependent cellular cytotoxicity ,Hepatology ,business.industry ,global B cells ,medicine.disease ,digestive system diseases ,HBV-ALF, HBV-induced acute liver failure ,Immunology ,biology.protein ,Human medicine ,PD-1, programmed cell death 1 ,business ,hepatitis B virus - Abstract
Summary: 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.
- Published
- 2022