Figure 4.

Rituximab-mediated cell killing of CD20 expressing B-cells. (Top left) Binding of rituximab to CD20 can directly trigger apoptosis through both caspase-dependent and -independent mechanisms that are still not fully characterized. (Top right) Bound rituximab can recruit the C1 complex triggering the classical complement cascade which leads to insertion of the membrane attack complex (MAC) and ultimately leads to cell lysis, also known as complement-dependent cytotoxicity (CDC). (Bottom left) Bound rituximab can recruit natural killer cells via recognition by the FcγRIII leading to antibody-dependent cell-mediated cytotoxicity (ADCC). This facilitates release of perforin, which assembles into membrane compromising pores in the target cell, and granzyme B, which enters the target cell and triggers apoptosis by cleaving caspases and potentially by other methods. (Bottom right) Macrophages recognize CD20 bound rituximab through various Fcγ receptors which leads to antibody-dependent phagocytosis (ADP) of the target cell.