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Auto-Antibody Production During Experimental Atherosclerosis in ApoE-/- Mice.
- Source :
- Frontiers in Immunology; 7/9/2021, Vol. 12, p1-10, 10p
- Publication Year :
- 2021
-
Abstract
- 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<superscript>-/-</superscript> Aid<superscript>-/-</superscript> 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<superscript>-/-</superscript> Aid<superscript>-/-</superscript> mice compared to ApoE<superscript>-/-</superscript> mice. Rigorous analysis of serum antibodies revealed both ApoE<superscript>-/-</superscript> and ApoE<superscript>-/-</superscript> Aid<superscript>-/-</superscript> 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<superscript>-/-</superscript> Aid<superscript>-/-</superscript> 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<superscript>-/-</superscript> 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- IMMUNOGLOBULIN G
ATHEROSCLEROTIC plaque
APOLIPOPROTEIN E
MICE
B cells
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 12
- Database :
- Complementary Index
- Journal :
- Frontiers in Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 151367324
- Full Text :
- https://doi.org/10.3389/fimmu.2021.695220