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B cell depletion reduces the development of atherosclerosis in mice

By Hafid Ait-Oufella, Olivier Herbin, Jean-David Bouaziz, Christoph J. Binder, Catherine Uyttenhove, Ludivine Laurans, Soraya Taleb, Emily Van Vré, Bruno Esposito, José Vilar, Jérôme Sirvent, Jacques Van Snick, Alain Tedgui, Thomas F. Tedder and Ziad Mallat

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-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

Topics: Brief Definitive Report
Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2916123
Provided by: PubMed Central

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