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Cutting Edge: BAFF Overexpression Reduces Atherosclerosis via TACI-Dependent B Cell Activation.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2016 Dec 15; Vol. 197 (12), pp. 4529-4534. Date of Electronic Publication: 2016 Nov 11. - Publication Year :
- 2016
-
Abstract
- Patients with systemic lupus erythematosus exhibit accelerated atherosclerosis, a chronic inflammatory disease of the arterial wall. The impact of B cells in atherosclerosis is controversial, with both protective and pathogenic roles described. For example, natural IgM binding conserved oxidized lipid epitopes protect against atherosclerosis, whereas anti-oxidized low-density lipoprotein (oxLDL) IgG likely promotes disease. Because BAFF promotes B cell class-switch recombination and humoral autoimmunity, we hypothesized that excess BAFF would accelerate atherosclerosis. In contrast, BAFF overexpression markedly reduced hypercholesterolemia and atherosclerosis in hyperlipidemic mice. BAFF-mediated atheroprotection required B cells and was associated with increased protective anti-oxLDL IgM. Surprisingly, high-titer anti-oxLDL IgM production and reduced atherosclerosis was dependent on the BAFF family receptor transmembrane activator and CAML interactor. In summary, we identified a novel role for B cell-specific, BAFF-dependent transmembrane activator and CAML interactor signals in atherosclerosis pathogenesis, of particular relevance to the use of BAFF-targeted therapies in systemic lupus erythematosus.<br />Competing Interests: The authors have declared that no conflict of interest exists<br /> (Copyright © 2016 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Autoantibodies blood
B-Cell Activating Factor genetics
Cells, Cultured
Humans
Immunoglobulin Class Switching
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Transmembrane Activator and CAML Interactor Protein genetics
Adaptor Proteins, Signal Transducing metabolism
Atherosclerosis immunology
B-Cell Activating Factor metabolism
B-Lymphocytes immunology
Lupus Erythematosus, Systemic immunology
Transmembrane Activator and CAML Interactor Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 197
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 27837104
- Full Text :
- https://doi.org/10.4049/jimmunol.1601198