BAFF over-expression reduces atherosclerosis via TACI-dependent B cell activation

• Published in: The Journal of immunology (1950) 2016-11, Vol.197 (12), p.4529-4534
• Main Authors: Jackson, Shaun W., Scharping, Nicole E., Jacobs, Holly M., Wang, Shari, Chait, Alan, Rawlings, David J.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1601198

Patients with SLE 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, while anti-oxidized low-density lipoprotein (oxLDL) IgG likely promotes disease. Since B cell activating factor of the TNF family (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 (TACI). In summary, we identified a novel role for B cell-specific, BAFF-dependent TACI signals in atherosclerosis pathogenesis, of particular relevance to the use of BAFF-targeted therapies in SLE.