UC San Diego

The clearance of dying cells is critical for maintaining tissue homeostasis, the prevention of autoimmunity, and the control of inflammation. The body produces billions of apoptotic cells (ACs) everyday, which normally are cleared by cells of the innate immune system, such as dendritic cells. These phagocytic cells recognize markers on the AC surface. If there is inefficient clearance, these cells progress to secondary necrosis and release pro- inflammatory factors, which can lead to inflammatory responses and autoimmune diseases. Numerous studies have shown that natural antibodies (NAbs) recognize ACs, but our understanding of their role in immune responses is limited. To evaluate whether antibodies are important for enhancing the phagocytosis of dying cells, mice were immunized with ACs to induce increased levels of anti-AC antibodies. An AC-binding assay showed that post- immunization sera had increased levels of both IgM and IgG antibodies binding to the surface of ACs, but not healthy cells, which was also seen with the NAb T15 IgM that recognizes phosphorylcholine determinants. To determine whether IgG antibodies are essential for apoptotic clearance, sera from AC immunized mice were depleted of IgG by passage on a protein-G column. In a phagocytic AC clearance assay, IgM antibodies were shown to be primarily responsible in aiding phagocytic cells to clear ACs, and there was no essential role for IgG in the process. Therefore, the results showed that IgM-natural antibodies, the T15 NAb and IgM antibodies induced by AC immunization, recognize apoptotic cells and enhance the ability of immature dendritic cells to phagocytose these cells.