title: B-Cell Depletion Promotes Aortic Infiltration of Immunosuppressive Cells and Is Protective of Experimental Aortic Aneurysm.
abstract: B-cell depletion therapy is widely used for treatment of cancers and autoimmune diseases. B cells are abundant in abdominal aortic aneurysms (AAA); however, it is unknown whether B-cell depletion therapy affects AAA growth. Using experimental models of murine AAA, we aim to examine the effect of B-cell depletion on AAA formation.
  
  
  
  Wild-type or apolipoprotein E-knockout mice were treated with mouse monoclonal anti-CD20 or control antibodies and subjected to an elastase perfusion or angiotensin II infusion model to induce AAA, respectively. Anti-CD20 antibody treatment significantly depleted B1 and B2 cells, and strikingly suppressed AAA growth in both models. B-cell depletion resulted in lower circulating IgM levels, but did not affect the levels of IgG or cytokine/chemokine levels. Although the total number of leukocyte remained unchanged in elastase-perfused aortas after anti-CD20 antibody treatment, the number of B-cell subtypes was significantly lower. Interestingly, plasmacytoid dendritic cells expressing the immunomodulatory enzyme indole 2,3-dioxygenase were detected in the aortas of B-cell-depleted mice. In accordance with an increase in indole 2,3-dioxygenase+ plasmacytoid dendritic cells, the number of regulatory T cells was higher, whereas the expression of proinflammatory genes was lower in aortas of B-cell-depleted mice. In a coculture model, the presence of B cells significantly lowered the number of indole 2,3-dioxygenase+ plasmacytoid dendritic cells without affecting total plasmacytoid dendritic cell number.
  
  
  
  The present results demonstrate that B-cell depletion protects mice from experimental AAA formation and promotes emergence of an immunosuppressive environment in aorta.
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
authors.forename: Basil
authors.initials: B
authors.lastname: Schaheen
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Downs
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
authors.forename: Vlad
authors.initials: V
authors.lastname: Serbulea
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
authors.forename: Camila C P
authors.initials: CC
authors.lastname: Almenara
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
authors.forename: Michael
authors.initials: M
authors.lastname: Spinosa
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
authors.forename: Gang
authors.initials: G
authors.lastname: Su
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
authors.forename: Yunge
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
authors.forename: Prasad
authors.initials: P
authors.lastname: Srikakulapu
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
authors.forename: Cherié
authors.initials: C
authors.lastname: Butts
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
authors.forename: Coleen A
authors.initials: CA
authors.lastname: McNamara
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
authors.forename: Norbert
authors.initials: N
authors.lastname: Leitinger
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
authors.forename: Gilbert R
authors.initials: GR
authors.lastname: Upchurch
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville. am5bv@virginia.edu.
authors.forename: Akshaya K
authors.initials: AK
authors.lastname: Meher
authors.affiliation: From the Departments of Surgery (B.S., E.A.D., M.S., G.S., Y.Z., G.R.U., A.K.M., G.A.), Pharmacology (V.S., C.C.P.A., N.L., A.K.M.), and Robert M. Berne Cardiovascular Research Center (P.S., C.A.M.N.), University of Virginia, Charlottesville; Biogen Idec, Cambridge, MA (C.B.); Department of Molecular Physiology and Biological Physics (G.R.U.) and Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
authors.forename: Gorav
authors.initials: G
authors.lastname: Ailawadi
mesh_terms: D000804:Angiotensin II; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D020022:Genetic Predisposition to Disease; D007075:Immunoglobulin M / Q000097:blood; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010196:Pancreatic Elastase; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D018951:Antigens, CD20; D001057:Apolipoproteins E; D015415:Biomarkers; D016207:Cytokines; D007075:Immunoglobulin M; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018836:Inflammation Mediators; D000804:Angiotensin II; D010196:Pancreatic Elastase
keywords: B1 and B2 cells; abdominal aortic aneurysm; anti-CD20 treatment; plasmacytoid dendritic cells; regulatory T cell