Home LiteratureArticle Details
PMID: 10862788 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 105 ·No. 12 ·2000-06-00 ·Pages 1731-40

Shaw PX, Hörkkö S, Chang MK, Curtiss LK, Palinski W, Silverman GJ, Witztum JL

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.

MeSH Terms
Amino Acid Sequence Animals Apolipoproteins E/deficiency,genetics Apoptosis/immunology Arteriosclerosis/genetics,immunology,pathology Autoantibodies/genetics,immunology B-Lymphocytes/immunology Base Sequence DNA Primers Gene Rearrangement Genes, Immunoglobulin Immunoglobulin Heavy Chains/genetics Immunoglobulin Idiotypes/genetics,physiology Immunoglobulin Light Chains/genetics Immunoglobulin M/physiology Lipoproteins, LDL/immunology Mice Mice, Knockout Molecular Sequence Data Phospholipid Ethers/immunology Sequence Alignment Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid
Chemicals
1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine Apolipoproteins E Autoantibodies DNA Primers Immunoglobulin Heavy Chains Immunoglobulin Idiotypes Immunoglobulin Light Chains Immunoglobulin M Lipoproteins, LDL Phospholipid Ethers oxidized low density lipoprotein
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Shaw P X
Department of Medicine, University of California, San Diego, La Jolla, California, USA. The Scripps Research Institute, La Jolla, California, USA.
Hörkkö S
Chang M K
Curtiss L K
Palinski W
Silverman G J
Witztum J L
References (31)
31 references, click to expand
  1. Heavy-chain class switch does not terminate somatic mutation.
    J Exp Med. 1990 Aug 1;172(2):531-6 PMID: 2115570
  2. Monoclonal vs. heterogeneous anti-H-8 antibodies in the analysis of the anti-phosphorylcholine response in BALB/c mice.
    Eur J Immunol. 1981 Nov;11(11):877-83 PMID: 7035186
  3. T cell-dependent antibody production by Ly-1 B cells.
    Ann N Y Acad Sci. 1992 May 4;651:328-35 PMID: 1376052
  4. Antigen binding and idiotype analysis of antibodies obtained after electroporation of heavy and light chain genes encoding phosphocholine-specific antibodies: a model for T15-idiotype dominance.
    J Exp Med. 1992 Dec 1;176(6):1637-43 PMID: 1460422
  5. Origin of murine B cell lineages.
    Annu Rev Immunol. 1993;11:501-38 PMID: 8476571
  6. Anti-phosphorylcholine antibodies of the T15 idiotype are optimally protective against Streptococcus pneumoniae.
    J Exp Med. 1982 Oct 1;156(4):1177-85 PMID: 7153709
  7. Rat anti-T15 monoclonal antibodies with specificity for VH- and VH-VL epitopes.
    Mol Immunol. 1984 Oct;21(10):961-7 PMID: 6209566
  8. Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL.
    Arterioscler Thromb. 1994 Jan;14(1):32-40 PMID: 7506053
  9. ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis. Demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum.
    Arterioscler Thromb. 1994 Apr;14(4):605-16 PMID: 7511933
  10. Immunization of low density lipoprotein (LDL) receptor-deficient rabbits with homologous malondialdehyde-modified LDL reduces atherogenesis.
    Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):821-5 PMID: 7846059
  11. Increased autoantibody titers against epitopes of oxidized LDL in LDL receptor-deficient mice with increased atherosclerosis.
    Arterioscler Thromb Vasc Biol. 1995 Oct;15(10):1569-76 PMID: 7583529
  12. Cloning of monoclonal autoantibodies to epitopes of oxidized lipoproteins from apolipoprotein E-deficient mice. Demonstration of epitopes of oxidized low density lipoprotein in human plasma.
    J Clin Invest. 1996 Aug 1;98(3):800-14 PMID: 8698873
  13. Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein.
    J Clin Invest. 1996 Aug 1;98(3):815-25 PMID: 8698874
  14. Oxidized phosphatidylcholines that modify proteins. Analysis by monoclonal antibody against oxidized low density lipoprotein.
    J Biol Chem. 1996 Dec 27;271(52):33208-17 PMID: 8969177
  15. An unbiased analysis of V(H)-D-J(H) sequences from B-1a, B-1b, and conventional B cells.
    J Immunol. 1997 Feb 1;158(3):1175-86 PMID: 9013957
  16. The epitopes for some antiphospholipid antibodies are adducts of oxidized phospholipid and beta2 glycoprotein 1 (and other proteins).
    Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10356-61 PMID: 9294215
  17. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions.
    J Clin Invest. 1997 Dec 1;100(11):2680-90 PMID: 9389731
  18. B-1 cell development: evidence for an uncommitted immunoglobulin (Ig)M+ B cell precursor in B-1 cell differentiation.
    J Exp Med. 1998 Apr 20;187(8):1325-34 PMID: 9547343
  19. The dual phases of the response to neonatal exposure to a VH family-restricted staphylococcal B cell superantigen.
    J Immunol. 1998 Nov 15;161(10):5720-32 PMID: 9820554
  20. Immunization of LDL receptor-deficient mice with homologous malondialdehyde-modified and native LDL reduces progression of atherosclerosis by mechanisms other than induction of high titers of antibodies to oxidative neoepitopes.
    Arterioscler Thromb Vasc Biol. 1998 Dec;18(12):1972-82 PMID: 9848892
  21. Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins.
    J Clin Invest. 1999 Jan;103(1):117-28 PMID: 9884341
  22. Phosphorylcholine: friend or foe of the immune system?
    Immunol Today. 1999 Mar;20(3):125-9 PMID: 10203703
  23. Monoclonal antibodies against oxidized low-density lipoprotein bind to apoptotic cells and inhibit their phagocytosis by elicited macrophages: evidence that oxidation-specific epitopes mediate macrophage recognition.
    Proc Natl Acad Sci U S A. 1999 May 25;96(11):6353-8 PMID: 10339591
  24. The chosen few? Positive selection and the generation of naive B lymphocytes.
    Immunity. 1999 May;10(5):493-502 PMID: 10367895
  25. Positive selection of natural autoreactive B cells.
    Science. 1999 Jul 2;285(5424):113-6 PMID: 10390361
  26. B cell antigen receptor specificity and surface density together determine B-1 versus B-2 cell development.
    J Exp Med. 1999 Aug 16;190(4):471-7 PMID: 10449518
  27. All T15 Id-positive antibodies (but not the majority of VHT15+ antibodies) are produced by peritoneal CD5+ B lymphocytes.
    Int Immunol. 1990;2(6):515-20 PMID: 1707658
  28. The three-dimensional structure of a phosphorylcholine-binding mouse immunoglobulin Fab and the nature of the antigen binding site.
    Proc Natl Acad Sci U S A. 1974 Nov;71(11):4298-302 PMID: 4530984
  29. The frequency of phosphorylcholine-specific B cells in conventional and germfree BALB/C mice.
    J Immunol. 1975 Apr;114(4):1354-8 PMID: 1078833
  30. Clonal nature of the immune response to phosphocholine. VII. Evidence throughout inbred mice for molecular similarities among antibodies bearing the T15 idiotype.
    J Immunol. 1980 Aug;125(2):551-8 PMID: 7391569
  31. IgG antibodies to phosphorylcholine exhibit more diversity than their IgM counterparts.
    Nature. 1981 May 7;291(5810):29-34 PMID: 7231520
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI8472
Published
2000-06-00
Pages
1731-40
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC378505
Subset
IM
Grants
NIAID NIH HHS · R01 AI040305 · United States
NHLBI NIH HHS · HL-56989 · United States
NHLBI NIH HHS · R01 HL057505 · United States
NIAID NIH HHS · R01 AI-40305 · United States
NHLBI NIH HHS · P50 HL056989 · United States
NHLBI NIH HHS · HL57505 · United States
Corrections
CommentIn
PMID: 10862783
External Links
PubMed source DOI: 10.1172/JCI8472 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2