Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8.
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.
Kranich
Jan
J
Institute of Neuropathology, University Hospital of Zurich, 8091 Zurich, Switzerland.
Krautler
Nike Julia
NJ
Heinen
Ernst
E
Polymenidou
Magdalini
M
Bridel
Claire
C
Schildknecht
Anita
A
Huber
Christoph
C
Kosco-Vilbois
Marie H
MH
Zinkernagel
Rolf
R
Miele
Gino
G
Aguzzi
Adriano
A
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000954:Antigens, Surface / Q000235:genetics*; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology; D016026:Bone Marrow Transplantation; D003433:Crosses, Genetic; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology*; D020566:Dendritic Cells, Follicular / Q000166:cytology / Q000502:physiology*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D017493:Leukocyte Common Antigens / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008894:Milk Proteins / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics; D017464:Receptors, Complement 3d / Q000276:immunology
D000906:Antibodies; D000954:Antigens, Surface; D017931:DNA Primers; C490919:Mfge8 protein, mouse; D008894:Milk Proteins; D017464:Receptors, Complement 3d; D012313:RNA; D017493:Leukocyte Common Antigens