title: B cell depletion reduces the development of atherosclerosis in mice.
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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 970, Paris Cardiovascular Research Center, 75015 Paris, France.
authors.forename: Hafid
authors.initials: H
authors.lastname: Ait-Oufella
authors.forename: Olivier
authors.initials: O
authors.lastname: Herbin
authors.forename: Jean-David
authors.initials: JD
authors.lastname: Bouaziz
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Binder
authors.forename: Catherine
authors.initials: C
authors.lastname: Uyttenhove
authors.forename: Ludivine
authors.initials: L
authors.lastname: Laurans
authors.forename: Soraya
authors.initials: S
authors.lastname: Taleb
authors.forename: Emily
authors.initials: E
authors.lastname: Van Vré
authors.forename: Bruno
authors.initials: B
authors.lastname: Esposito
authors.forename: José
authors.initials: J
authors.lastname: Vilar
authors.forename: Jérôme
authors.initials: J
authors.lastname: Sirvent
authors.forename: Jacques
authors.initials: J
authors.lastname: Van Snick
authors.forename: Alain
authors.initials: A
authors.lastname: Tedgui
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D018951:Antigens, CD20 / Q000276:immunology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation; D002784:Cholesterol / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics; D012850:Sinus of Valsalva / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D001057:Apolipoproteins E; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D020381:Interleukin-17; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein; D007371:Interferon-gamma; D002784:Cholesterol