Mechanisms of action of anti-CD20 antibodies. (Top panel) Apoptosis of malignant B-cell clones occurs upon cross-linking of rituximab-CD20 complexes in the lipid rafts. This activates signaling pathways involving the Src kinases and their regulatory molecules. Complement-mediated cytolysis involves the ability of anti-CD20 immunoglobulin G1 bound to their antigen to bind C1 and trigger the classical complement pathway. Antibody-dependent cell cytotoxicity requires interaction between the Fc portion of rituximab and appropriate receptors on effector cells. (Bottom panel) Another possible mechanism by which rituximab could promote the destruction of malignant B-cell clones is the restoration of the protective antitumoral response. The destruction of the nonmalignant B cells endowed with immune-regulatory properties could facilitate the development of antitumoral T-cell clones.