Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity.
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.
Shaw
P X
PX
Department of Medicine, University of California, San Diego, La Jolla, California, USA. The Scripps Research Institute, La Jolla, California, USA.
Hörkkö
S
S
Chang
M K
MK
Curtiss
L K
LK
Palinski
W
W
Silverman
G J
GJ
Witztum
J L
JL
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
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