The autoreactivity of anti-phosphorylcholine antibodies for atherosclerosis-associated neo-antigens and apoptotic cells.
Abs specific for phosphorylcholine (PC) are known to contribute to the immune defense against a variety of microbial infections. To assess for other types of binding interactions, we performed surveys of anti-PC Abs of diverse biologic origins and structural diversity and demonstrated a common autoreactivity for oxidatively modified low density lipoprotein and other oxidation-specific structures containing PC-Ags. We also found that cells undergoing apoptosis sequentially express a range of oxidation-specific neo-self PC determinants. Whereas natural Abs to PC recognized cells at early stages of apoptosis, by contrast, an IgG anti-PC Ab, representative of a T cell-dependent response, recognized PC determinants primarily associated with late stages of apoptosis. Cumulatively, these results demonstrate a fundamental paradigm in which Abs from both the innate and the T cell-dependent tiers of the B cell compartment recognize a minimal molecular motif arrayed both on microbes and as neo-self Ags linked to atherosclerosis and autoimmune disease.
Shaw
Peter X
PX
Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA. pshaw@ucsd.edu
Goodyear
Carl S
CS
Chang
Mi-Kyung
MK
Witztum
Joseph L
JL
Silverman
Gregg J
GJ
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology*; D001161:Arteriosclerosis / Q000276:immunology* / Q000473:pathology*; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D006241:Haptens / Q000276:immunology / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D010767:Phosphorylcholine / Q000276:immunology*; D011817:Rabbits; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D017152:Antibodies, Antiphospholipid; D001324:Autoantigens; D000939:Epitopes; D006241:Haptens; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D010767:Phosphorylcholine