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 generatedLdlr-/-chimeras transplanted with bone marrow fromAicda-/-or wild-type (WT) mice, fed a HFD for 14 weeks. Decreased B cell maturation inLdlr-/-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 inLdlr–/-Aicda-/-compared withLdlr-/-WT animals. Importantly,Ldlr-/-Aicda-/-mice had reduced atherosclerotic lesion area (0.20 ± 0.03mm2) compared withLdlr-/-WT (0.30 ± 0.04mm2, 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.