We have recently identified conventional B2 cells as atherogenic and B1a cells as atheroprotective in hypercholesterolemic
ApoE(-/-) mice. Here, we examined the development of
atherosclerosis in BAFF-R deficient
ApoE(-/-) mice because B2 cells but not B1a cells are selectively depleted in BAFF-R deficient mice. We fed BAFF-R(-/-)
ApoE(-/-) (BaffR.
ApoE DKO) and BAFF-R(+/+)
ApoE(-/-) (
ApoE KO) mice a high fat diet (HFD) for 8-weeks. B2 cells were significantly reduced by 82%, 81%, 94%, 72% in blood, peritoneal fluid, spleen and peripheral lymph nodes respectively; while B1a cells and non-B lymphocytes were unaffected. Aortic atherosclerotic lesions assessed by
oil red-O stained-
lipid accumulation and CD68+ macrophage accumulation were decreased by 44% and 50% respectively. B cells were absent in atherosclerotic lesions of BaffR.
ApoE DKO mice as were
IgG1 and
IgG2a immunoglobulins produced by B2 cells, despite low but measurable numbers of B2 cells and
IgG1 and
IgG2a immunoglobulin concentrations in plasma. Plasma
IgM and
IgM deposits in atherosclerotic lesions were also reduced. BAFF-R deficiency in
ApoE(-/-) mice was also associated with a reduced expression of
VCAM-1 and fewer macrophages, dendritic cells, CD4+ and CD8+ T cell infiltrates and PCNA+ cells in lesions. The expression of proinflammatory
cytokines, TNF-α, IL1-β and proinflammatory
chemokine MCP-1 was also reduced.
Body weight and plasma cholesterols were unaffected in BaffR.
ApoE DKO mice. Our data indicate that B2 cells are important contributors to the development of
atherosclerosis and that targeting the BAFF-R to specifically reduce atherogenic B2 cell numbers while preserving atheroprotective B1a cell numbers may be a potential therapeutic strategy to reduce
atherosclerosis by potently reducing
arterial inflammation.