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B-cell receptors (BCRs) specific for influenza hemagglutinin (HA) epitopes are membrane-bound immunoglobulins on the surface of B lymphocytes that play a critical role in the adaptive immune response to influenza (Nature, 2013). These receptors are designed to recognize and bind to specific antigenic determinants (epitopes) on the hemagglutinin protein, the primary surface glycoprotein of the influenza virus (Wikipedia, 2024). Upon antigen binding, the BCR complex initiates intracellular signaling that drives B-cell activation, proliferation, and differentiation into plasma cells that secrete neutralizing antibodies and long-lived memory B cells (NIH, 2016). In the context of drug development, these receptors are the primary targets of influenza vaccines, which aim to stimulate the production of antibodies that can block viral entry (Frontiers in Immunology, 2016). A major challenge in targeting these BCRs is the high rate of antigenic drift in the HA protein, which necessitates annual vaccine updates, and the phenomenon of original antigenic sin, where the immune response is biased toward previously encountered viral strains (Journal of Virology, 2019). Additionally, some studies suggest that the influenza virus can directly infect HA-specific B cells through the BCR, potentially suppressing the early immune response (Nature, 2013).
Antigen-mediated B-cell receptor activation and subsequent induction of humoral immunity.
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