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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}inserm.fr OR zm255{at}medschl.cam.ac.uk
Abstract:
B cell depletion significantly reduces the burden of severalimmune-mediated diseases. However, B cell activation has beenuntil now associated with a protection against atherosclerosis,suggesting that B cell–depleting therapies would enhancecardiovascular risk. We unexpectedly show that mature B celldepletion using a CD20-specific monoclonal antibody inducesa significant reduction of atherosclerosis in various mousemodels of the disease. This treatment preserves the productionof natural and potentially protective anti–oxidized low-densitylipoprotein (oxLDL) IgM autoantibodies over IgG type anti-oxLDLantibodies, and markedly reduces pathogenic T cell activation.B cell depletion diminished T cell–derived IFN- secretionand enhanced production of IL-17; neutralization of the latterabrogated CD20 antibody–mediated atheroprotection. Theseresults challenge the current paradigm that B cell activationplays an overall protective role in atherogenesis and identifynew antiatherogenic strategies based on B cell modulation.
H. Ait-Oufella and O. Herbin contributed equally to this paper.
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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. 
