The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20071019
The Journal of Experimental Medicine, Vol. 205, No. 6, 1293-1302
The Rockefeller University Press, 0022-1007 $30.00
© Kranich et al.
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BRIEF DEFINITIVE REPORT

 Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8

Jan Kranich1, Nike Julia Krautler1, Ernst Heinen3, Magdalini Polymenidou1, Claire Bridel1, Anita Schildknecht2, Christoph Huber4, Marie H. Kosco-Vilbois5, Rolf Zinkernagel2, Gino Miele6, and Adriano Aguzzi1

1 Institute of Neuropathology and 2 Institute of Experimental Immunology, University Hospital of Zurich, 8091 Zurich, Switzerland
3 Institute of Human Histology, University of Liège, 4000 Liège, Belgium
4 Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
5 NovImmune SA, 1211 Geneva, Switzerland
6 Translational Medicine Research Collaboration, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, UK

CORRESPONDENCE Adriano Aguzzi: Adriano.Aguzzi{at}usz.ch

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 (TBM{phi}s). 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 TBM{phi}s. However, Mfge8–/– TBM{phi}s 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 TBM{phi}-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 TBM{phi}-mediated corpse removal, and their malfunction may be involved in autoimmunity.

© 2008 Kranich et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jgp.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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