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

Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8.

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1
Institute of Neuropathology, University Hospital of Zurich, 8091 Zurich, Switzerland.

Abstract

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.

PMID:
18490487
PMCID:
PMC2413028
DOI:
10.1084/jem.20071019
[Indexed for MEDLINE]
Free PMC Article
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