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J. Exp. Med. 207 (8): 1579-1587

Copyright © 2010 by the Rockefeller University Press.

Brief Definitive Report

B cell depletion reduces the development of atherosclerosis in mice

Hafid Ait-Oufella1,2, Olivier Herbin1, Jean-David Bouaziz3,4, Christoph J. Binder5,6, Catherine Uyttenhove7,8, Ludivine Laurans1, Soraya Taleb1, Emily Van Vré1, Bruno Esposito1, José Vilar1, Jérôme Sirvent1, Jacques Van Snick7,8, Alain Tedgui1, Thomas F. Tedder3, , and Ziad Mallat1,9

1 Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 970, Paris Cardiovascular Research Center, 75015 Paris, France
2 Assistance Publique–Hôpitaux de Paris, Saint-Antoine Hospital, 75012 Paris, France
3 Department of Immunology, Duke University Medical Center, Durham, NC 27710
4 INSERM, Unit 976, Skin Research Center, Saint Louis Hospital, 75475 Paris, France
5 Center for Molecular Medicine of the Austrian Academy of Sciences and 6 Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria
7 Ludwig Institute for Cancer Research and 8 Cellular Genetics Unit, Université de Louvain, 1200 Brussels, Belgium
9 Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ, England, UK

CORRESPONDENCE Ziad Mallat: ziad.mallat{at} OR zm255{at}

Abstract: B cell depletion significantly reduces the burden of several immune-mediated diseases. However, B cell activation has been until now associated with a protection against atherosclerosis, suggesting that B cell–depleting therapies would enhance cardiovascular risk. We unexpectedly show that mature B cell depletion using a CD20-specific monoclonal antibody induces a significant reduction of atherosclerosis in various mouse models of the disease. This treatment preserves the production of natural and potentially protective anti–oxidized low-density lipoprotein (oxLDL) IgM autoantibodies over IgG type anti-oxLDL antibodies, and markedly reduces pathogenic T cell activation. B cell depletion diminished T cell–derived IFN-{gamma} secretion and enhanced production of IL-17; neutralization of the latter abrogated CD20 antibody–mediated atheroprotection. These results challenge the current paradigm that B cell activation plays an overall protective role in atherogenesis and identify new antiatherogenic strategies based on B cell modulation.

H. Ait-Oufella and O. Herbin contributed equally to this paper.

Abbreviations: Apoe, apolipoprotein E • Ldlr, LDL receptor • oxLDL, oxidized low-density lipoprotein

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