Abstract
The immune response to oxidized LDL (OxLDL) may play an important role in atherogenesis. Working with apoE-deficient mice, we isolated a panel of OxLDL-specific B-cell lines that secrete IgM Abs that specifically bind to oxidized phospholipids such as 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine (POVPC). These Abs block uptake of OxLDL by macrophages, recognize similar oxidation-specific epitopes on apoptotic cells, and are deposited in atherosclerotic lesions. The Abs were found to be structurally and functionally identical to classic "natural" T15 anti-PC Abs that are of B-1 cell origin and are reported to provide optimal protection from virulent pneumococcal infection. These findings suggest that there has been natural selection for B-1 cells secreting oxidation-specific/T15 antibodies, both for their role in natural immune defense and for housekeeping roles against oxidation-dependent neodeterminants in health and disease.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Apolipoproteins E / deficiency
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Apolipoproteins E / genetics
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Apoptosis / immunology*
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Arteriosclerosis / genetics
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Arteriosclerosis / immunology*
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Arteriosclerosis / pathology
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Autoantibodies / genetics
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Autoantibodies / immunology*
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B-Lymphocytes / immunology*
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Base Sequence
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DNA Primers
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Gene Rearrangement
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Genes, Immunoglobulin
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin Idiotypes / genetics
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Immunoglobulin Idiotypes / physiology*
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Immunoglobulin Light Chains / genetics
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Immunoglobulin M / physiology
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Lipoproteins, LDL / immunology*
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Phospholipid Ethers / immunology
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Sequence Alignment
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Sequence Homology, Amino Acid
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Sequence Homology, Nucleic Acid
Substances
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1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine
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Apolipoproteins E
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Autoantibodies
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DNA Primers
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Immunoglobulin Heavy Chains
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Immunoglobulin Idiotypes
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Immunoglobulin Light Chains
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Immunoglobulin M
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Lipoproteins, LDL
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Phospholipid Ethers
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oxidized low density lipoprotein