Hemagglutinin-specific B-cell receptor (HA-specific BCR) (HA-specific BCR)

Hemagglutinin-specific B-cell receptors (BCRs) are membrane-bound immunoglobulins on the surface of B lymphocytes that recognize and bind to specific epitopes on the influenza virus hemagglutinin (HA) protein (Tesini et al., 2019). These receptors are central to the adaptive immune response, as their engagement by HA antigens—either from natural infection or vaccination—triggers B-cell activation and the subsequent production of neutralizing antibodies (Source 1.1.3). BCRs can target the highly variable globular head of HA, providing strain-specific immunity, or the more conserved stem region, which is the focus of universal vaccine development for broad-spectrum protection (Source 1.3.1). Upon binding, the BCR initiates intracellular signaling cascades that lead to B-cell proliferation and differentiation into long-lived memory B cells and plasma cells (Source 1.3.3). Interestingly, research has shown that these receptors can also serve as an entry point for the influenza virus, potentially leading to the infection and death of the very B cells intended to provide protection (Dougan et al., 2013). Therapeutic strategies primarily involve the use of vaccines to stimulate these BCRs, though challenges such as original antigenic sin and viral mutation (antigenic drift) complicate the maintenance of long-term immunity (Source 1.1.4, 1.4.2). Monitoring the frequency and repertoire of these receptors serves as a critical biomarker for evaluating vaccine efficacy and the breadth of the immune response (Frasca et al., 2011; Nellore et al., 2023).

Other names

Influenza hemagglutinin-specific B-cell receptorHA-reactive B-cell receptorAnti-HA BCRHA-specific B-cell antigen receptor

Vaccine antigens or viral hemagglutinin bind to the B-cell receptor, inducing receptor clustering and intracellular signaling through kinases such as Lyn and Syk (Tesini et al., 2019). This signaling cascade leads to B-cell activation, proliferation, and differentiation into antibody-secreting plasma cells and memory B cells (Source 1.1.3). In some instances, the BCR can also facilitate the internalization of the influenza virus into the B cell itself, leading to cell death (Dougan et al., 2013).