CR2 (CD21) is a transmembrane glycoprotein that serves as a critical receptor linking innate and adaptive immunity. CR2 primarily functions as a complement receptor, binding C3 fragments including iC3b, C3dg, and C3d that are covalently attached to antigens 12. This interaction lowers the threshold for B cell activation by bringing complement-opsonized antigens into direct contact with B lymphocytes 1. CR2 is predominantly expressed on B lymphocytes and follicular dendritic cells, where it modulates B-cell growth and differentiation 32. Beyond complement binding, CR2 serves as the cellular receptor for Epstein-Barr virus (EBV), with the viral glycoprotein gp350 utilizing the same binding site as complement C3d through molecular mimicry involving arginine residues 42. Recent research demonstrates that complement-CR2 signaling shapes B cell subset differentiation during cancer chemotherapy, with this pathway being triggered by immunogenic cell death 5. CR2 deficiencies are associated with systemic lupus erythematosus and common variable immunodeficiency, highlighting its importance in immune regulation 3. The receptor's dual role in complement-mediated immunity and viral pathogenesis makes it a significant target for understanding autoimmune diseases and developing antiviral therapeutics.