Spatial multi-omics reveals novel vascular adipocyte and B cell biology in human abdominal aortic aneurysm

Authors

Meher, A. K., Huang, W., Yamaguchi, D. J., Yin, C., Swyers, M. M., Dubis, G., Yang, L. V., Mannie, M. D., McNamara, C. A.

Abstract

Objective: Perivascular Adipose Tissue (PVAT), tertiary lymphoid structures (TLS), and the B lymphocytes they harbor have been implicated in regulating vascular diseases, including abdominal aortic aneurysm (AAA). Yet, the relationship of adipose tissue to TLS and B cell responses is poorly understood. Approach and Results: Here, we used a multi-omic approach to rigorously define the landscape of human AAA and characterize the adipocyte and TLS microenvironment with regard to B-cell responses to vascular antigens in human AAA and control non-aneurysmal abdominal aortas. Single-nucleus and single-cell RNA sequencing identified transcripts for lipogenesis, lipolysis, extracellular remodeling, haptotactic and chemotactic factors, with potential to recruit CD44+ leukocytes within AAAs. Immunohistology and Visium HD spatial transcriptomics revealed that at least two adipocyte types exist: one in the PVAT and another as isolated clusters in the medial-adventitial region in human AAAs but not in control aortas. Further characterization of these medial-adventitial adipocytes in the AAAs showed close association with TLSs. Mature TLSs recapitulated the organization of functional secondary lymphoid structures, with multiple B-cell follicles clustered to form a nodular structure partly covered by a layer of smooth muscle cells. The TLSs harbored isotype-switched B cells expressing IgG1, IgG3, or IgA, with dominant kappa chain usage and abundant IgG antibodies to aortic wall. Myeloid cells in AAA were implicated in promoting B cell effects, as they were the primary producers of B-cell activating factor (BAFF), a cytokine that promotes B cell infiltration, survival, and function. Conclusion: Altogether, our results support a novel model in which new adipocytes in the medial-adventitial layer produce factors that promote early TLS formation, and BAFF produced by myeloid cells promotes the survival and maturation of vascular wall-antigen-exposed B cells, leading to mature TLS formation, production of antibodies to AAA antigens, fueling inflammation and AAA growth.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 21 Oct 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.