Defects in the disposal of dying cells lead to autoimmunity.

The fast and efficient uptake of dying cells is of main importance to prevent contact of the immune system with intracellular autoantigens. Insufficient clearance of the latter is discussed to drive the humoral autoimmune response in systemic lupus erythematosus. Many adaptor molecules and receptors are involved in the recognition of dying cells. In this paper we focus on the involvement of phosphatidylserine, glycoproteins, and complement and DNaseI in the clearance of apoptotic and necrotic cells, respectively. Furthermore, extracellular danger signals released from necrotic cells are discussed and the uptake process of primary necrotic cells is investigated in detail. Last but not least, the character and origin of clearance defects observed in some systemic lupus erythematosus patients is presented.