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B-cell antigen receptors (BCRs) specific for orthopoxvirus antigens are specialized transmembrane protein complexes found on the surface of B lymphocytes that recognize and bind to specific proteins from viruses such as Variola (smallpox) and Monkeypox (Mpox) (PubMed: 36103501). These receptors are composed of a membrane-bound immunoglobulin (mIg) molecule that determines antigen specificity and a signaling heterodimer consisting of CD79A and CD79B (UniProt: P11912). Upon binding to viral surface antigens like L1, A27, or B5, the BCR undergoes conformational changes and clustering, which activates intracellular signaling pathways including the phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) (PubMed: 28250123). This activation leads to B-cell proliferation, affinity maturation, and differentiation into plasma cells that secrete high-affinity neutralizing antibodies, which are essential for clearing the infection and providing long-term immunity (PubMed: 15661914). In clinical medicine, these receptors are the primary targets of vaccines such as JYNNEOS and ACAM2000, which aim to elicit a protective BCR repertoire (CDC, 2022). Additionally, the study of these specific receptors is vital for the development of monoclonal antibody therapies and the evaluation of vaccine efficacy through the measurement of neutralizing antibody titers (PubMed: 18006601).
Vaccines provide orthopoxvirus antigens that bind to and cross-link specific B-cell antigen receptors, triggering a signaling cascade through CD79A/B and tyrosine kinases (e.g., Syk), which results in B-cell activation, clonal expansion, and the production of protective antibodies (PubMed: 28250123).
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