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Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity
Peter X. Shaw, … , Gregg J. Silverman, Joseph L. Witztum
Peter X. Shaw, … , Gregg J. Silverman, Joseph L. Witztum
Published June 15, 2000
Citation Information: J Clin Invest. 2000;105(12):1731-1740. https://doi.org/10.1172/JCI8472.
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Article

Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity

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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

Peter X. Shaw, Sohvi Hörkkö, Mi-Kyung Chang, Linda K. Curtiss, Wulf Palinski, Gregg J. Silverman, Joseph L. Witztum

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Figure 6

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T15 IgA recognizes apoptotic cells. FACS® analysis of T15 Ab and control...
T15 IgA recognizes apoptotic cells. FACS® analysis of T15 Ab and control IgA (C-IgA; nonspecific monoclonal) binding to apoptotic PAECs. (a) Apoptosis-induced PAECs were gated into two populations according to PI intensity and FSC as described (7). Region 2 (R2): normal cells and cells in very early apoptosis. Region 1 (R1): cells with dim and bright PI staining (apoptotic). (b) Binding of control IgA and T15 to R2 cells. (c) Binding of control IgA and T15 to R1 cells.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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