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CD21 (complement receptor 2, CR2) binds C3 complement fragments, especially its breakdown fragments, which remain covalently attached to complement activating surfaces or antigen. CD21 has important roles in uptake and retention of immunocomplexes, survival of memory B cells and in development and maintenance of the humoral response to T-dependent antigens. CD21 also serves as a key receptor for Epstein-Barr virus binding and is involved in targeting prions to folicular dendritic cells and expediting neuroinvasion following peripheral exposure to prions. A soluble form of the CD21 (sCD21) is shed from the lymphocyte surface and retains its ability to bind respective ligands. CD35 encodes a membrane glycoprotein found on peripheral blood cells, glomerular podocytes, and follicular dendritic cells. The protein is a receptor for complement components C3b and C4b and regulates the activity of the complement cascade. Variation in this protein is the basis of the Knops blood group system. The two most common alleles, F and S, differ by 8 exons and are thought to be the result of an unequal crossover event. A secreted form of the protein present in plasma has been described, but its full length nature has not been determined.
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