| First Author | Hutchinson MA | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 695220 | PubMed ID | 34305930 |
| Mgi Jnum | J:312586 | Mgi Id | MGI:6728985 |
| Doi | 10.3389/fimmu.2021.695220 | Citation | Hutchinson MA, et al. (2021) Auto-Antibody Production During Experimental Atherosclerosis in ApoE(-/-) Mice. Front Immunol 12:695220 |
| abstractText | Current models stipulate that B cells and antibodies function during atherosclerosis in two distinct ways based on antibody isotype, where IgM is protective and IgG is inflammatory. To examine this model, we generated ApoE(-/-) Aid(-/-) mice, which are unable to produce IgG antibodies due to the absence of activation-induced deaminase (AID) but maintain high plasma cholesterol due to the absence of apolipoprotein E (APOE). We saw a dramatic decrease in plaque formation in ApoE(-/-) Aid(-/-) mice compared to ApoE(-/-) mice. Rigorous analysis of serum antibodies revealed both ApoE(-/-) and ApoE(-/-) Aid(-/-) mice had substantially elevated titers of IgM antibodies compared to C57BL/6J controls, suggesting a more complex dynamic than previously described. Analysis of antigen specificity demonstrated that ApoE(-/-) Aid(-/-) mice had elevated titers of antibodies specific to malondialdehyde-oxidized low density lipoprotein (MDA-oxLDL), which has been shown to block macrophage recruitment into plaques. Conversely, ApoE(-/-) mice showed low levels of MDA-oxLDL specificity, but had antibodies specific to numerous self-proteins. We provide evidence for a hierarchical order of antibody specificity, where elevated levels of MDA-oxLDL specific IgM antibodies inhibit plaque formation. If the level of MDA-oxLDL specific IgM is insufficient, self-reactive IgM and IgG antibodies are generated against debris within the arterial plaque, resulting in increased inflammation and further plaque expansion. |
