| First Author | Ebrahimian T | Year | 2023 |
| Journal | Sci Rep | Volume | 13 |
| Issue | 1 | Pages | 8723 |
| PubMed ID | 37253865 | Mgi Jnum | J:353868 |
| Mgi Id | MGI:7487526 | Doi | 10.1038/s41598-023-35980-1 |
| Citation | Ebrahimian T, et al. (2023) B cell-specific knockout of AID protects against atherosclerosis. Sci Rep 13(1):8723 |
| abstractText | 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(2)) compared with Ldlr(-/-)WT (0.30 +/- 0.04mm(2), 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. |
