Hepatitis B virus-specific B-cell receptor (HBV-specific BCR)

Hepatitis B virus-specific B-cell receptors (HBV-specific BCRs) are membrane-bound immunoglobulins on the surface of B lymphocytes that specifically recognize viral antigens such as the Hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) (Salimzadeh et al., 2018, J Clin Invest). These receptors are essential for the initiation of the humoral immune response, as their engagement by viral epitopes triggers B-cell activation, proliferation, and differentiation into plasma cells that produce neutralizing antibodies (Burton & Mason, 2020, Nat Rev Gastroenterol Hepatol). In chronic hepatitis B (CHB) infection, HBV-specific B cells often enter a state of functional exhaustion or 'atypical' memory differentiation, characterized by the expression of inhibitory receptors like PD-1 and impaired antibody production (Le Bert et al., 2020, Gastroenterology). Therapeutic interventions, such as therapeutic vaccines (e.g., VBI-2601/BRII-179) and immune checkpoint inhibitors, are being developed to revitalize these BCR-mediated responses to achieve a functional cure, defined by sustained HBsAg loss (Zhang et al., 2022, Front Immunol). By restoring the activity of these receptors, the immune system can effectively clear circulating viral particles and infected hepatocytes. Furthermore, the specificity of these BCRs is being leveraged in the development of engineered B-cell therapies and as biomarkers for monitoring the restoration of host immunity during treatment.

Other names

HBV-specific B-cell receptors recognizing HBV envelope and other HBV epitopesHBsAg-specific B-cell receptorHBcAg-specific B-cell receptorHepatitis B virus-specific BCRHBV-specific B-lymphocyte receptor

Therapeutic vaccines and immunomodulators target HBV-specific BCRs to overcome B-cell exhaustion, promoting the expansion of antigen-specific B cells and their differentiation into plasma cells that secrete neutralizing anti-HBs antibodies (Salimzadeh et al., 2018).