Artery tertiary lymphoid organs control multi-layered territorialized atherosclerosis B cell responses in aged ApoE-/- mice

Srikakulapu, P. et al. (2016) Artery tertiary lymphoid organs control multi-layered territorialized atherosclerosis B cell responses in aged ApoE-/- mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 36, pp. 1174-1185. (doi:10.1161/ATVBAHA.115.306983) (PMID:27102965) (PMCID:PMC4894775)

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Abstract

Objective: Explore aorta B cell immunity in aged ApoE-/- mice. Approach and Results: Transcript maps, FACS, immunofluorescence analyses, cell transfers, and Ig-ELISPOT assays showed multi-layered 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 though intima plaques preferentially expressed molecules involved in non-B effector responses towards B cell-derived mediators, i.e. Fcgr3 (Cd16), Fcer1g (Cd23), and the C1q family. ATLOs promoted B cell recruitment. ATLO B-2 B cells included naïve, transitional, follicular, germinal center, switched IgG1+, IgA+, and IgE+ memory cells, plasmablasts, and long-lived plasma cells (PCs). ATLOs recruited large numbers of B-1 cells whose subtypes were skewed towards IL-10+ B-1b cells versus IL-10- B-1a cells. ATLO B-1 cells and PCs constitutively produced IgM and IgG and a fraction of PCs expressed IL-10. Moreover, ApoE-/- mice showed increased germinal center B cells in renal lymph nodes, IgM-producing PCs in the bone marrow, and higher IgM and anti-MDA-LDL IgG serum titers. Conclusions: ATLOs orchestrate dichotomic, territorialized, and multi-layered B cell responses in the diseased aorta; germinal center reactions indicate generation of autoimmune B cells within the diseased arterial wall during aging.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maffia, Dr Pasquale and Grassia, Dr Gianluca
Authors: Srikakulapu, P., Hu, D., Yin, C., Mohanta, S. K., Bontha, S. V., Peng, L., Beer, M., Weber, C., McNamara, C. A., Grassia, G., Maffia, P., Manz, R. A., and Habenicht, A. J.R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher:American Heart Association
ISSN:1079-5642
ISSN (Online):1524-4636
Published Online:21 April 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Arteriosclerosis, Thrombosis, and Vascular Biology 36:1174-1185
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
614711Defining innate and adaptive immune functions of plasmacytoid dendritic cells in atherosclerosis.Pasquale MaffiaBritish Heart Foundation (BHF)PG/12/81/29897III -IMMUNOLOGY