The follicular zones were enlarged. There were 2 to 3 times more lymphocytes in the spleens of the MFG-E8(-/-) mice. An increased number of IgG-producing cells were found in the spleen follicles. The female MFG-E8(-/-) mice spontaneously produced high titer of anti-antibodies anti-dsDNA and ANA at the age of week 40 but not at w10. Immunization female 10-week-old mice twice with KLH promoted ANA production 20 days later in MFG-E8(-/-) but not wild type mice. Immune complex deposition, hyper-cellularity of glomeruli, and proteinuria were observed in most female MFG-E8(-/-) mice at week 40. Therefore, inefficient engulfment of apoptotic B cells by might lead to lupus-like autoimmune disease. Kenichi et al. showed that masking phosphatidylserine by MFG-E8 mutant D89E, carrying a point mutation in RGD motif, inhibited not only the phagocytosis of apoptotic cells by macrophages of different origins but also the production of IL10 by thioglycollate-elicited peritoneal macrophages after phagocytosing apoptotic cells. When D89E MFG-E8 was injected into wild type mice intravenously, auto-antibodies were induced. The production of auto-antibodies was enhanced by co-injection of syngenic apoptotic cells. The auto-antibodies persisted for a long-term and IgG deposition on glomeruli took place. These results added in proof that the impairment of phagocytic clearance of apoptotic cells leads to auto-antibody production and autoimmune disease.In the past 4 years, a growing number of molecules were recognized as receptors for the PS exposed on the apoptotic cells. These molecules were capable of mediating phagocytic clearance, rendering anti-inflammatory cytokines in the phagocytes, and modulating T cell responses.