Potential anti-CD20 mAb effector mechanisms. (A) Fc-FcγR–dependent mechanisms. The Fc arm of anti-CD20 mAb recruits and activates FcγR-expressing immune effector cells, including macrophages and NK cells, which in turn eliminate the target cell by release of cytotoxic mediators in ADCC (NK cells and macrophages) or direct phagocytosis (macrophages). (B) CDC. Complement fixation occurs when C1q, the globular head of C1, binds the Fc portion of 2 IgG molecules, which triggers a series of enzymatic reactions that generate pores in the cell membrane (membrane attack complex) leading to cell lysis. (C) Direct PCD is induced primarily by type II anti-CD20 mAbs through an actin-dependent, lysosomal pathway after homotypic adhesion. (D) Adaptive cellular immunity. Anti-CD20 mAbs promote the uptake of tumor antigens by dendritic cells and cross-presentation to T cells, which differentiate into cytotoxic T cells that evoke an antitumor cellular immune response.