B cell-specific knockout of AID protects against atherosclerosis
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,...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-35980-1 |
| _version_ | 1797811537017044992 |
|---|---|
| author | Talin Ebrahimian France Dierick Vincent Ta Maria Kotsiopriftis Jonathan O’Connor Miranda Koren K. Mann Alexandre Orthwein Stephanie Lehoux |
| author_facet | Talin Ebrahimian France Dierick Vincent Ta Maria Kotsiopriftis Jonathan O’Connor Miranda Koren K. Mann Alexandre Orthwein Stephanie Lehoux |
| author_sort | Talin Ebrahimian |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T07:25:12Z |
| format | Article |
| id | doaj.art-46c5d8ed292f491ba4c713375be2a4b3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T07:25:12Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-46c5d8ed292f491ba4c713375be2a4b32023-06-04T11:25:21ZengNature PortfolioScientific Reports2045-23222023-05-011311810.1038/s41598-023-35980-1B cell-specific knockout of AID protects against atherosclerosisTalin Ebrahimian0France Dierick1Vincent Ta2Maria Kotsiopriftis3Jonathan O’Connor Miranda4Koren K. Mann5Alexandre Orthwein6Stephanie Lehoux7Lady Davis Institute for Medical ResearchLady Davis Institute for Medical ResearchLady Davis Institute for Medical ResearchLady Davis Institute for Medical ResearchLady Davis Institute for Medical ResearchLady Davis Institute for Medical ResearchLady Davis Institute for Medical ResearchLady Davis Institute for Medical ResearchAbstract 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.https://doi.org/10.1038/s41598-023-35980-1 |
| spellingShingle | Talin Ebrahimian France Dierick Vincent Ta Maria Kotsiopriftis Jonathan O’Connor Miranda Koren K. Mann Alexandre Orthwein Stephanie Lehoux B cell-specific knockout of AID protects against atherosclerosis Scientific Reports |
| title | B cell-specific knockout of AID protects against atherosclerosis |
| title_full | B cell-specific knockout of AID protects against atherosclerosis |
| title_fullStr | B cell-specific knockout of AID protects against atherosclerosis |
| title_full_unstemmed | B cell-specific knockout of AID protects against atherosclerosis |
| title_short | B cell-specific knockout of AID protects against atherosclerosis |
| title_sort | b cell specific knockout of aid protects against atherosclerosis |
| url | https://doi.org/10.1038/s41598-023-35980-1 |
| work_keys_str_mv | AT talinebrahimian bcellspecificknockoutofaidprotectsagainstatherosclerosis AT francedierick bcellspecificknockoutofaidprotectsagainstatherosclerosis AT vincentta bcellspecificknockoutofaidprotectsagainstatherosclerosis AT mariakotsiopriftis bcellspecificknockoutofaidprotectsagainstatherosclerosis AT jonathanoconnormiranda bcellspecificknockoutofaidprotectsagainstatherosclerosis AT korenkmann bcellspecificknockoutofaidprotectsagainstatherosclerosis AT alexandreorthwein bcellspecificknockoutofaidprotectsagainstatherosclerosis AT stephanielehoux bcellspecificknockoutofaidprotectsagainstatherosclerosis |