Article ; Online: B cell-specific knockout of AID protects against atherosclerosis
Scientific Reports, Vol 13, Iss 1, Pp 1-
2023 Volume 8
Abstract: Abstract 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 ... ...
| Abstract | Abstract 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 ± 0.03mm2) compared with Ldlr -/- 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. |
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| Keywords | Medicine ; R ; Science ; Q |
| Language | English |
| Publishing date | 2023-05-01T00:00:00Z |
| Publisher | Nature Portfolio |
| Document type | Article ; Online |
| Database | BASE - Bielefeld Academic Search Engine (life sciences selection) |
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