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Apoptotic cells expose phosphatidylserine and are swiftly engulfedby macrophages. Milk fat globule epidermal growth factor (EGF)factor 8 (MFG-E8) is a protein that binds to apoptotic cellsby recognizing phosphatidylserine and that enhances the engulfmentof apoptotic cells by macrophages. We report that tingible bodymacrophages in the germinal centers of the spleen and lymphnodes strongly express MFG-E8. Many apoptotic lymphocytes werefound on the MFG-E8–/– tingible body macrophages,but they were not efficiently engulfed. The MFG-E8–/–mice developed splenomegaly, with the formation of numerousgerminal centers, and suffered from glomerulonephritis as aresult of autoantibody production. These data demonstrate thatMFG-E8 has a critical role in removing apoptotic B cells inthe germinal centers and that its failure can lead to autoimmunediseases.
1 Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. 2 Department of Pathology, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. 3 Department of Cell Biology and Neuroscience, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. 4 Laboratory for Innate Cellular Immunity, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan. 5 Laboratory of Genetics, Integrated Biology Laboratories, Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan. 6 Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Osaka 565-0871, Japan.
* To whom correspondence should be addressed. E-mail: nagata{at}genetic.med.osaka-u.ac.jp.
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