A B-1 Cell Immunization-Based Strategy to Prevent Atherogenesis

Karina Payerhin

Abstract


Cardiovascular disease is a serious health issue responsible for approximately 17.3 million deaths globally each year. Atherosclerosis, the leading contributor to cardiovascular disease, is characterized by the accumulation of low-density lipoprotein (LDL) in blood vessels with subsequent oxidation leading to oxidation specific epitopes (OSE) that are recognized by the body as foreign. Macrophages take up these oxidized lipids and contribute to inflammation, leading to plaque formation. B-1 cells are a subset of B-lymphocytes that produce IgM antibodies against these OSE, preventing oxidized lipid uptake by macrophages. The aim of this project is to determine if increasing the number of B-1 cells and immunizing with oxidized lipids could increase production of IgM antibodies and ameliorate the development and progression of atherosclerosis. To accomplish this, B-1 cells from donor mice were adoptively transferred into atherosclerosis-prone mice (ApoE-/-). Half of the mice were immunized with two types of OSE (malondialdehyde-modified LDL (MDA-LDL) and pneumococcal polysaccharide-3 (PPS-3)), and the other half were treated with a control injection. Serum from all mice was collected at five different time points, and levels of IgM to OSE are being measured. The mice were euthanized at 16 weeks after the adoptive transfer, and aortas and aortic roots were collected and will be analyzed for plaque deposition. The study tests the hypothesis that both increasing B-1 cell numbers and immunization with OSE will increase serum IgM to OSE and decrease plaque deposition. These data may lead to the design of an immunization-based approach to treat and prevent human atherosclerosis.


Keywords


Immunization, atherosclerosis, B-cells

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