title: Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity.
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.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California, USA. The Scripps Research Institute, La Jolla, California, USA.
authors.forename: P X
authors.initials: PX
authors.lastname: Shaw
authors.forename: S
authors.initials: S
authors.lastname: Hörkkö
authors.forename: M K
authors.initials: MK
authors.lastname: Chang
authors.forename: L K
authors.initials: LK
authors.lastname: Curtiss
authors.forename: W
authors.initials: W
authors.lastname: Palinski
authors.forename: G J
authors.initials: GJ
authors.lastname: Silverman
authors.forename: J L
authors.initials: JL
authors.lastname: Witztum
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D017209:Apoptosis / Q000276:immunology*; D001161:Arteriosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000502:physiology*; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000502:physiology; D008077:Lipoproteins, LDL / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010742:Phospholipid Ethers / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: C400184:1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine; D001057:Apolipoproteins E; D001323:Autoantibodies; D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D010742:Phospholipid Ethers; C099252:oxidized low density lipoprotein