Objective— The goal of this study was to assess the role of B-cell activating factor (BAFF) receptor in ­B-­cell regulation of atherosclerosis. Methods and Results— Male LDL ­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 low-density lipoprotein. 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.