Distinct balance of apoptotic cell clearance. Normal clearance of apoptotic cells (left side, blue) involves sequential signals and plays an important role in tolerance induction and maintenance. Inflammatory clearance of apoptotic cells (right side, red) involves multi-inflammatory stimuli, breaks down tolerance, and drives autoimmunity including systemic lupus erythematosus. Blue blebs: early apoptotic cells modify surface markers and release signals to regulate chemotaxis and phagocytosis. Red blebs: later apoptotic cells and necrotic cells lose the cell membrane integrity, leading to the release of danger signals and modified autoantigens. dRP S19, dimer of ribosomal protein S19; HMGB1, high mobility group box 1; IL, interleukin; LTF, lactoferrin; MP, microparticle; NET, neutrophil extracellular trap; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PS, phosphatidylserine; TGF-β, transforming growth factor beta.