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Open Access Green as soon as Postprint is submitted to ZB.
Artery tertiary lymphoid organs control multilayered territorialized atherosclerosis B-cell responses in aged ApoE-/- mice.
Arterioscler. Thromb. Vasc. Biol. 36, 1174-1185 (2016)
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OBJECTIVE: Explore aorta B-cell immunity in aged ITALIC! ApoE (-/-) mice. APPROACH AND RESULTS: Transcript maps, fluorescence-activated cell sorting, immunofluorescence analyses, cell transfers, and Ig-ELISPOT assays showed multilayered atherosclerosis B-cell responses in artery tertiary lymphoid organs (ATLOs). Aging-associated aorta B-cell-related transcriptomes were identified, and transcript atlases revealed highly territorialized B-cell responses in ATLOs versus atherosclerotic lesions: ATLOs showed upregulation of bona fide B-cell genes, including Cd19, Ms4a1 (Cd20), Cd79a/b, and Ighm although intima plaques preferentially expressed molecules involved in non-B effector responses toward B-cell-derived mediators, that is, Fcgr3 (Cd16), Fcer1g (Cd23), and the C1q family. ATLOs promoted B-cell recruitment. ATLO B-2 B cells included naive, transitional, follicular, germinal center, switched IgG1(+), IgA(+), and IgE(+) memory cells, plasmablasts, and long-lived plasma cells. ATLOs recruited large numbers of B-1 cells whose subtypes were skewed toward interleukin-10(+) B-1b cells versus interleukin-10(-) B-1a cells. ATLO B-1 cells and plasma cells constitutively produced IgM and IgG and a fraction of plasma cells expressed interleukin-10. Moreover, ApoE (-/-) mice showed increased germinal center B cells in renal lymph nodes, IgM-producing plasma cells in the bone marrow, and higher IgM and anti-MDA-LDL IgG serum titers. CONCLUSIONS: ATLOs orchestrate dichotomic, territorialized, and multilayered B-cell responses in the diseased aorta; germinal center reactions indicate generation of autoimmune B cells within the diseased arterial wall during aging.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
B-lymphocytes ; Aging ; Atherosclerosis ; Germinal Center ; Inflammation; Laser-capture Microdissection; Lived Plasma-cells; Hypercholesterolemic Mice; Regulatory Function; Autoimmune-disease; Adaptive Immunity; Nzb/w Mice; Major Site; Null Mice; Depletion
Language
english
Publication Year
2016
HGF-reported in Year
2016
ISSN (print) / ISBN
1079-5642
e-ISSN
1524-4636
Quellenangaben
Volume: 36,
Issue: 6,
Pages: 1174-1185
Publisher
Lippincott Williams & Wilkins
Publishing Place
Philadelphia
Reviewing status
Peer reviewed
Institute(s)
Research Unit Molecular Immune Regulation (AMIR)
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Immune Response and Infection
PSP Element(s)
G-501712-001
WOS ID
WOS:000378298100016
PubMed ID
27102965
Erfassungsdatum
2016-05-10