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Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity
Peter X. Shaw, Sohvi Hörkkö, Mi-Kyung Chang, Linda K. Curtiss, Wulf Palinski, Gregg J. Silverman, Joseph L. Witztum
Peter X. Shaw, Sohvi Hörkkö, Mi-Kyung Chang, Linda K. Curtiss, Wulf Palinski, Gregg J. Silverman, Joseph L. Witztum
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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 7

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Presence of T15 idiotypic Abs in atherosclerotic lesions. Atheroscleroti...
Presence of T15 idiotypic Abs in atherosclerotic lesions. Atherosclerotic segments of aorta of LDLR–/– mice were prepared and stained as described in Methods. Epitopes recognized are indicated by a red color; the nuclei are counterstained with methyl green. (a) Section immunostained with a combined anti-mouse IgG/IgM antisera, indicating the presence of Ig in lesion. (b) An adjacent section immunostained with biotinylated AB1-2 (anti-T15 idiotype). A similar pattern demonstrates that some Ig deposited in the lesion represents Abs of the T15 idiotype. (c) An adjacent section stained with biotinylated nonimmune IgG was free of specific staining.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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