Mechanisms of rituximab-mediated cell death. Rituximab coated B cells are killed by at least 4 different mechanisms. (A) Binding of rituximab to CD20 on B cell surface causes activation of the complement cascade, which generates the membrane attack complex (MAC) that can directly induce B-cell lysis by complement-mediated cytotoxicity (CDC). (B) Binding of rituximab allows interaction with NK cells via Fc receptors III (FcRIII), which leads to antibody-dependent cell-mediated cytotoxicity (ADCC). (C) The Fc portion of rituximab and the deposited complement fragments allow for recognition by both FcR and complement receptors on macrophages, which lead to phagocytosis and ADCC. (D) The crosslinking of several molecules of rituximab and CD20 in the lipid raft determine the interaction of these complexes with elements of a signaling pathway involving Src kinases that mediate direct apoptosis.