Antigen-naive IgM-producing B cells are atheroprotective, whereas mature B cells producing class-switched antibodies promote atherosclerosis. Activation-induced cytidine deaminase (AID), which mediates class switch recombination (CSR), would thus be expected to foster atherosclerosis. Yet, AID also plays a major role in the establishment of B cell tolerance. We sought to define whether AID affects atherosclerotic plaque formation. We generated Ldlr chimeras transplanted with bone marrow from Aicda or wild-type (WT) mice, fed a HFD for 14 weeks. Decreased B cell maturation in Ldlr Aicda mice was demonstrated by 50% reduction in splenic and aortic BAFFR expression, a key signaling component of B2 cell maturation. This was associated with increased plasma IgM in Ldlr Aicda compared with Ldlr WT animals. Importantly, Ldlr Aicda mice had reduced atherosclerotic lesion area (0.20 ± 0.03mm ) compared with Ldlr WT (0.30 ± 0.04mm , P < 0.05), although no differences in plaque composition were noted between groups. In addition, immunofluorescence analysis revealed increased splenic B and T cell areas independent of cell number. AID depletion directly inhibits atherosclerotic plaque formation.