Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8

J Exp Med. 2008 Jun 9;205(6):1293-302. doi: 10.1084/jem.20071019. Epub 2008 May 19.


The secreted phosphatidylserine-binding protein milk fat globule epidermal growth factor 8 (Mfge8) mediates engulfment of apoptotic germinal center B cells by tingible-body macrophages (TBMphis). Impairment of this process can contribute to autoimmunity. We show that Mfge8 is identical to the mouse follicular dendritic cell (FDC) marker FDC-M1. In bone-marrow chimeras between wild-type and Mfge8(-/-) mice, all splenic Mfge8 was derived from FDCs rather than TBMphis. However, Mfge8(-/-) TBMphis acquired and displayed Mfge8 only when embedded in Mfge8(+/+) stroma, or when situated in lymph nodes draining exogenous recombinant Mfge8. These findings indicate a licensing role for FDCs in TBMphi-mediated removal of excess B cells. Lymphotoxin-deficient mice lacked FDCs and splenic Mfge8, and suffer from autoimmunity similar to Mfge8(-/-) mice. Hence, FDCs facilitate TBMphi-mediated corpse removal, and their malfunction may be involved in autoimmunity.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antigens, Surface / genetics*
  • Apoptosis / physiology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / physiology
  • Bone Marrow Transplantation
  • Crosses, Genetic
  • DNA Primers
  • Dendritic Cells / immunology*
  • Dendritic Cells, Follicular / cytology
  • Dendritic Cells, Follicular / physiology*
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Leukocyte Common Antigens / immunology
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Milk Proteins / genetics*
  • Milk Proteins / metabolism
  • RNA / genetics
  • Receptors, Complement 3d / immunology


  • Antibodies
  • Antigens, Surface
  • DNA Primers
  • Mfge8 protein, mouse
  • Milk Proteins
  • Receptors, Complement 3d
  • RNA
  • Leukocyte Common Antigens