title: B regulatory cells are increased in hypercholesterolaemic mice and protect from lesion development via IL-10.
abstract: Whilst innate B1-B cells are atheroprotective, adaptive B2-B cells are considered pro-atherogenic. Different subsets of B regulatory cells (B(reg)) have been described. In experimental arthritis and lupus-like disease, B(reg) are contained within the CD21(hi)CD23(hi)CD24(hi) B cell pool. The existence and role of B(reg) in vascular disease is not known. We sought to investigate the existence, identity and location of B(reg) in vascular disease. The representation of B2-B cell subsets in the spleens and lymph nodes (LNs) of Apolipoprotein E(-/-) (ApoE(-/-)) mice compared to controls was characterised by flow cytometry. Additionally, we utilised a model of neointima formation based on the placement of a perivascular collar around the carotid artery in ApoE(-/-) mice to ascertain whether B cells and B cell subsets confer protection against lesion development. Adoptive transfer of B cells was performed from wild type or genetically modified mice. We showed that CD21(hi)CD23(hi)CD24(hi) B cells are unexpectedly increased in the draining LNs of ApoE(-/-) mice. Adoptive transfer of LN-derived B2-B cells or purified CD21(hi)CD23(hi)CD24(hi) B cells to syngeneic mice reduced lesion size and inflammation without changing serum cholesterol levels. Follicular B2-B cells did not confer protection. IL-10 blockade or transfer of IL10-deficient B cells prevented LN-derived B cell-mediated protection. This is the first identification of a specific LN-derived B2-B(reg) subset that confers IL-10 mediated protection from neointima formation. This may open the way for immune modulatory approaches in cardiovascular disease.
authors.forename: Asa C
authors.initials: AC
authors.lastname: Strom
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cross
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Cole
authors.forename: Paul A
authors.initials: PA
authors.lastname: Blair
authors.forename: Christoph
authors.initials: C
authors.lastname: Leib
authors.forename: Michael E
authors.initials: ME
authors.lastname: Goddard
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Rosser
authors.forename: Inhye
authors.initials: I
authors.lastname: Park
authors.forename: Anna
authors.initials: A
authors.lastname: Hultgårdh Nilsson
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
authors.forename: Claudia
authors.initials: C
authors.lastname: Mauri
authors.affiliation: Claudia Monaco, Kennedy Institute of Rheumatology, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK, Tel.: + 44 1865 612 636, Fax: + 44 1865 612 601, E-mail: claudia.monaco@kennedy.ox.ac.uk.
authors.forename: Claudia
authors.initials: C
authors.lastname: Monaco
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D051927:CD24 Antigen / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D002339:Carotid Arteries / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002340:Carotid Artery Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020212:Carotid Artery Injuries / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006937:Hypercholesterolemia / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058426:Neointima; D010641:Phenotype; D065840:Protective Factors; D017464:Receptors, Complement 3d / Q000276:immunology / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; D051927:CD24 Antigen; D019013:CD40 Antigens; C497890:Cd24a protein, mouse; C556062:IL10 protein, mouse; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D016753:Interleukin-10
keywords: B regulatory cells; Immunity; atherosclerosis; interleukins; vascular disease