Autoimmune Disease and Impaired Uptake of Apoptotic Cells in MFG-E8-Deficient Mice

TLDR

Apoptotic cells expose phosphatidylserine and are rapidly cleared by macrophages, a process facilitated by the protein MFG‑E8 which binds phosphatidylserine and promotes engulfment. In MFG‑E8‑deficient mice, tingible body macrophages accumulate uncleared apoptotic lymphocytes, leading to splenomegaly, expanded germinal centers, and glomerulonephritis from autoantibody production, underscoring MFG‑E8’s essential role in clearing apoptotic B cells to prevent autoimmunity.

Abstract

Apoptotic cells expose phosphatidylserine and are swiftly engulfed by macrophages. Milk fat globule epidermal growth factor (EGF) factor 8 (MFG-E8) is a protein that binds to apoptotic cells by recognizing phosphatidylserine and that enhances the engulfment of apoptotic cells by macrophages. We report that tingible body macrophages in the germinal centers of the spleen and lymph nodes strongly express MFG-E8. Many apoptotic lymphocytes were found on the MFG-E8-/- tingible body macrophages, but they were not efficiently engulfed. The MFG-E8-/- mice developed splenomegaly, with the formation of numerous germinal centers, and suffered from glomerulonephritis as a result of autoantibody production. These data demonstrate that MFG-E8 has a critical role in removing apoptotic B cells in the germinal centers and that its failure can lead to autoimmune diseases.