Abstract 1518: Exacerbated Atherosclerosis in CD36 Null Mice may be due to Decreased Titers of IgM Antibodies that Bind Oxidized Low-Density Lipoproteins
Natural antibodies (Nab) like T15/E06 bind oxidized phospholipids. These same Nab are associated with protection against the development of atherosclerosis. Nab arise early in development and play a role in host homeostasis. B-1 cell expression of the IgM Nab E06 was shown to react with oxidation-derived epitopes on apoptotic cells and oxidized (ox) low-density lipoprotein (LDL) and thereby participates in their removal. Because CD36 is a macrophage scavenger receptor responsible for the removal of oxLDL from the circulation, yet CD36 null mice develop severe lesions throughout the aortic tree, we hypothesized that CD36 could influence the production of atheroprotective IgM. LDL receptor knock-out mice were irradiated and reconstituted with bone marrow (BM) from either CD36 null mice (n=15) or C57BL/6 wild type mice (n=15). Weight and total plasma cholesterol was measured every fourth week throughout a 16 week high-fat diet (HFD) feeding study. Afterwards the extent of lesions were analyzed and the plasma levels of antibodies against oxLDL epitopes were measured. The plasma titers of IgM that bound malondialdehyde and cupper oxidized LDL were increased (264% and 408%) in control mice that received C57BL/6 BM. Mice receiving CD36 null BM had low basal levels of IgM and a significantly lower HFD-induced increase in the IgM response (151% and 162%). Mice receiving CD36 null BM also developed significantly larger (p<0.001) lesion areas in the en face aorta compared to mice receiving C57BL/6 BM. Therefore, a decrease in plasma IgM titers specific for ox epitopes of LDL was accompanied by increased atherosclerosis in LDL receptor null chimeras reconstituted with CD36 null BM.