Getting away with murder: how does the BCL-2 family of proteins kill with immunity?

Abstract

The adult human body produces approximately one million white blood cells every second. However, only a small fraction of the cells will survive because the majority is eliminated through a genetically controlled form of cell death known as apoptosis. This review places into perspective recent studies pertaining to the BCL-2 family of proteins as critical regulators of the development and function of the immune system, with particular attention on B cell and T cell biology. Here we discuss how elegant murine model systems have revealed the major contributions of the BCL-2 family in establishing an effective immune system. Moreover, we highlight some key regulatory pathways that influence the expression, function, and stability of individual BCL-2 family members, and discuss their role in immunity. From lethal mechanisms to more gentle ones, the final portion of the review discusses the nonapoptotic functions of the BCL-2 family and how they pertain to the control of immunity.