CD35, also known as complement receptor 1 (CR1), is a transmembrane complement regulatory protein that is widely expressed on hematopoietic cells. It cooperates with both CD21 and CR3/MAC-1 in the binding and internalization of particles and immune complexes that are opsonized with complement components C3b, C3i, and C4b. It also binds and internalizes particles opsonized with complement factor C1q or mannose binding lectin (MBL). CD35 protects the cell from complement-mediated lysis by serving as a cofactor for Factor I and inhibiting the C3 and C5 convertases. Erythrocyte-expressed CD35 mediates the hepatic clearance of complement-opsonized immune complexes. On lymphocytes, CD35 inhibits the activation-induced proliferation of T cells and B cells. Mice deficient in both CD21 and CD35 exhibit normal B cell development but severely compromised germinal center development, antibody production, and establishment of protective microbial immunity.