Uncontrolled lymphoproliferation is a characteristic feature of lymphomas and leukemias. Nonmalignant lymphoproliferative diseases are also observed in humans as well as in lpr (lymphoproliferation) and gld (generalized lymphadenopathy) mice. The discoveries that spontaneous mutations of Fas (APO-1/CD95) or its ligand (FasL) were associated with the lpr and gld phenotypes led to a satisfying explanation as to how deficiency of a pivotal lymphocyte apoptotic pathway (Fas–FasL) caused accumulation of activated lymphocytes in the peripheral immune system 1. A second important consequence of the failure to delete activated cells of the immune system is systemic autoimmunity—which can be explained by the persistence of potentially self-reactive T cells and, most likely, antigen-presenting cells in the peripheral immune system 2.
The remarkable strides made in defining the cellular biochemistry of apoptosis over the last 5 years have led to several predictions...
