Related Experiment Video
Updated: Mar 22, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Artery Tertiary Lymphoid Organs Control Multilayered Territorialized Atherosclerosis B-Cell Responses in Aged ApoE-/-
Prasad Srikakulapu1, Desheng Hu1, Changjun Yin1
1From the Cardiovascular Research Center, Department of Medicine (P.S., C.A.M.), Department of Surgery (S.V.B.), University of Virginia, Charlottesville; Institute for Immunology (D.H.) and Institute for Cardiovascular Prevention (C.Y., S.K.M., C.W., A.J.R.H.), Ludwig-Maximilians-University, Munich, Germany; Institute of Molecular Immunology, Helmholtz-Zentrum München, Oberschleißheim, Germany (D.H.); Department for Information Technology, University of Jena, Jena University Hospital, Jena, Germany (M.B.); Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (G.G., P.M.); BHF Centre for Excellence in Vascular Science and Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (P.M.); Department of Pharmacy, University of Naples Federico II, Naples, Italy (P.M.); Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany (R.A.M.); and Department of Traditional Chinese Medicine, Medical College of Xiamen University, Xiamen University, Xiamen, China (L.P.).
Objective:
Explore aorta B-cell immunity in aged apolipoprotein E-deficient (ApoE(-/-)) mice.
Approach And Results:
Transcript maps, fluorescence-activated cell sorting, immunofluorescence analyses, cell transfers, and Ig-ELISPOT (enzyme-linked immunospot) 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 (malondialdehyde-modified low-density lipoprotein) 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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