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

Authors

Chuankai Zhang, Xi Zhang, Yi Ran, Zhihua Wang, Liping Li, Shu Wang, Junjie Zheng, Yixin Zhang, Ting Sun, Yutao Li, Shu Lu, Mingyang Hong, Zhe Ma, Sabine Steffens, Michael Hristov, Xavier Blanchet, Jingpu Zhu, Xinwen Dou, Xinyi Deng, Klaus Dornmair, Desheng Hu, Shibojyoti Lahiri, Axel Imhof, Nadja Sachs, Lars Maegdefessel, Jingyi Xiao, Jianning Zhang, Yan Wang, Hua Hong, Livia Habenicht, Xinyu Weng, Junbo Ge, Christian Weber, Donato Santovito, Rachael Bashford-Rogers, Sarajo K Mohanta, Klaus Ley, Andreas J R Habenicht, Changjun Yin

Published in

Nature cardiovascular research. Sep 07, 2026. Epub Sep 07, 2026.

Abstract

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.

PMID:
42706439
Bibliographic data and abstract were imported from PubMed on 08 Sep 2026.

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