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

Hepatitis B virus-specific B-cell receptors (HBV-BCRs) are membrane-bound immunoglobulins on the surface of B lymphocytes that recognize and bind to specific epitopes of the Hepatitis B virus, including the surface antigen (HBsAg), core antigen (HBcAg), and viral polymerase [1, 2]. These receptors are essential for the initiation of the humoral immune response, as their engagement by viral antigens triggers B-cell activation, clonal expansion, and differentiation into antibody-secreting plasma cells or memory B cells [3, 4]. In patients with chronic hepatitis B (CHB), HBsAg-specific BCRs frequently exhibit a state of functional exhaustion or an "atypical" memory phenotype, characterized by the expression of inhibitory receptors such as PD-1 and a failure to produce sufficient neutralizing antibodies [1, 2, 4]. In contrast, HBcAg-specific BCRs often remain more functional and are found at higher frequencies in the circulation [3]. Therapeutic strategies currently under investigation aim to modulate these receptors through therapeutic vaccines like VBI-2601 (BRII-179) to restore B-cell function or by utilizing high-affinity BCR sequences to develop monoclonal antibodies such as VIR-3434 for passive immunotherapy [4, 6]. Understanding the specificity and functionality of the HBV-BCR repertoire is a key component in the pursuit of a functional cure for chronic HBV infection [3]. [1] Salimzadeh, L., et al. (2018). Journal of Experimental Medicine. [2] Burton, A. R., et al. (2018). Journal of Clinical Investigation. [3] Le Bert, N., et al. (2020). Gastroenterology. [4] Poonia, B., et al. (2020). Seminars in Immunopathology. [5] Weimer, T., et al. (1990). Journal of Virology. [6] Gane, E., et al. (2021). VIR-3434 Clinical Data.

Other names

HBV-specific BCRHBsAg-specific B-cell receptorHBcAg-specific B-cell receptorHBV polymerase-specific B-cell receptorAnti-HBV B-cell receptor

Binding of HBV antigens to the BCR triggers B-cell activation, antigen internalization, and presentation to T cells, leading to the production of neutralizing antibodies and the establishment of immunological memory.