BAFF (B Cell Activating Factor) Receptor Deficiency Reduces the Development of Atherosclerosis in Mice

Abstract

Objective- To assess the role of BAFF (B cell activating factor) receptor in B cell regulation of atherosclerosis. Methods and Results- Male low-density lipoprotein receptor-deficient mice (Ldlr$^{-/-}$) were lethally irradiated and reconstituted with either wild type or BAFF receptor (BAFF-R)-deficient bone marrow. After 4 weeks of recovery, mice were put on a high fat diet for 6 or 8 weeks. BAFF-R deficiency in bone marrow cells led to a marked reduction of conventional mature B2 cells but did not affect the B1a cell subtype. This was associated with a significant reduction of dendritic cell activation and T cell proliferation along with a reduction of IgG antibodies against malondialdehyde-modified LDL. In contrast, serum IgM type antibodies were preserved. Interestingly, BAFF-R deficiency was associated with a significant reduction in atherosclerotic lesion development and reduced numbers of plaque T cells. Selective BAFF-R deficiency on B cells led to a similar reduction in lesion size and T cell infiltration but in contrast did not affect dendritic cell activation. Conclusion- BAFF-R deficiency in mice selectively alters mature B2 cell-dependent cellular and humoral immune responses, and limits the development of atherosclerosis.