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Zhang, C.* ; Zhang, X.* ; Ran, Y.* ; Wang, Z.* ; Li, L.* ; Wang, S.* ; Zheng, J.* ; Zhang, Y.* ; Sun, T.* ; Li, Y.* ; Lu, S.* ; Hong, M.* ; Ma, Z.* ; Steffens, S. ; Hristov, M.* ; Blanchet, X.* ; Zhu, J.* ; Dou, X.* ; Deng, X.* ; Dornmair, K.* ; Hu, D.* ; Lahiri, S.* ; Imhof, A.* ; Sachs, N.* ; Mäegdefessel, L.* ; Xiao, J.* ; Zhang, J.* ; Wang, Y.* ; Hong, H.* ; Habenicht, L.* ; Weng, X.* ; Ge, J.* ; Weber, C.* ; Santovito, D.* ; Bashford-Rogers, R.* ; Mohanta, S.K.* ; Ley, K.* ; Habenicht, A.J.R.* ; Yin, C.*

Artery tertiary lymphoid organs encode a pathogenic high-affinity autoantibody−autoantigen pair in atherosclerosis.

Nat. Cardio. Res. 5, 869-890 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Artery tertiary lymphoid organs (ATLOs) emerge in atherosclerosis, which is a chronic inflammatory artery disease with an autoimmune component. However, whether disease-relevant autoimmune B cells emerge in ATLOs remains unknown. In this study, we isolate germinal center (GC) B cells from ATLOs and lymph nodes from healthy and atherosclerosis-burdened mice, expression clone 60 autoantibodies and screen them for arterial wall reactivity. ATLO GC B cell-derived autoantibodies skew to atherosclerosis-relevant autoantigens versus their counterparts in lymph nodes of both genotypes. One ATLO GC B cell-derived autoantibody (termed A6) binds to histone 2B (H2B) with high affinity. Both vaccination with H2B and adoptive transfer of A6 accelerate atherosclerosis, revealing a pathogenic autoantibody-autoantigen pair. Mechanistically, ATLOs specifically show both distorted B cell activation and immune tolerance checkpoint-regulating gene expression profiles. In a human cohort, circulating anti-H2B antibody titers positively correlate with aortic calcification in humans. We suggest that ATLOs harbor a dysregulated immune tolerance environment permissive for autoreactive B cells that express pathogenic autoantibodies promoting atherosclerosis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Germinal Center ; Autoantibody ; Clone (java Method) ; Immune System ; Antibody ; Lymph ; Autoimmunity ; Lymphatic System
ISSN (print) / ISBN 2731-0590
e-ISSN 2731-0590
Journal Nature Cardiovascular Research
Quellenangaben Volume: 5, Issue: 9, Pages: 869-890 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)
Grants Guangdong Innovative and Entrepreneurial Research Team Program
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
China Postdoctoral Science Foundation
National Natural Science Foundation of China (National Science Foundation of China)
Deutsche Forschungsgemeinschaft (German Research Foundation)