quarta-feira, 7 de julho de 2010

Células B e aterosclerose

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
+ Author Affiliations
1Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 970, Paris Cardiovascular Research Center, 75015 Paris, France
2Assistance Publique–Hôpitaux de Paris, Saint-Antoine Hospital, 75012 Paris, France
3Department of Immunology, Duke University Medical Center, Durham, NC 27710
4INSERM, Unit 976, Skin Research Center, Saint Louis Hospital, 75475 Paris, France
5Center for Molecular Medicine of the Austrian Academy of Sciences and 6Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria
7Ludwig Institute for Cancer Research and 8Cellular Genetics Unit, Université de Louvain, 1200 Brussels, Belgium
9Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ, England, UK
CORRESPONDENCE Ziad Mallat: ziad.mallat@inserm.fr OR zm255@medschl.cam.ac.uk
H. Ait-Oufella and O. Herbin contributed equally to this paper.

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-γ 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.

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