The autoreactivity of anti-phosphorylcholine antibodies for atherosclerosis-associated neo-antigens and apoptotic cells.

Abstract

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.

• Authors: Peter X Shaw, Carl S Goodyear, Mi-Kyung Chang, Joseph L Witztum, Gregg J Silverman
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 170 Issue 12 Pg. 6151-7 (Jun 15 2003) ISSN: 0022-1767 [Print] United States
• PMID: 12794145 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Antiphospholipid
• Autoantigens
• Epitopes
• Haptens
• Lipoproteins, LDL
• oxidized low density lipoprotein
• Phosphorylcholine

Topics

• Animals
• Antibodies, Antiphospholipid (metabolism)
• Apoptosis (immunology)
• Arteriosclerosis (immunology, pathology)
• Autoantigens (immunology, metabolism)
• Binding Sites, Antibody
• Epitopes (immunology, metabolism)
• Haptens (immunology, metabolism)
• Lipoproteins, LDL (immunology, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Oxidation-Reduction
• Phosphorylcholine (immunology)
• Rabbits
• T-Lymphocyte Subsets (immunology, metabolism)
• Thymus Gland (cytology, immunology, metabolism)