Natural IgM antibodies against oxidation-specific epitopes.
BACKGROUND
Natural antibodies (NAbs) are mostly antibodies of the IgM isotype with germline or close to germline encoded variable regions that provide them with specificity for both microbial and altered self antigens. Thus, natural IgM possess an important function in the first line defense against invading pathogens and in tissue homeostasis by regulating the clearance of cellular debris.


RESULTS
Oxidation-specific epitopes represent prominent examples of stress-induced altered self, as they are generated ubiquitously as a consequence of lipid peroxidation during many physiological and pathological situations, and are found on the membranes of apoptotic cells. Importantly, oxidation-specific epitopes are dominant targets of natural IgM antibodies, indicating an important role for natural IgM in their clearance and the neutralization of their pro-inflammatory properties.


CONCLUSIONS
These findings and the insights they provide into the ability of NAbs in mediating host homeostasis in health and diseases, including atherosclerosis and other chronic inflammatory diseases, will be discussed.
Binder
Christoph J
CJ
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria. christoph.binder@meduniwien.ac.at
D019264:Adoptive Transfer; D000447:Aldehydes / Q000276:immunology; D000818:Animals; D000918:Antibody Specificity; D050197:Atherosclerosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation; D000939:Epitopes / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007075:Immunoglobulin M / Q000276:immunology*; D015227:Lipid Peroxidation / Q000276:immunology; D008077:Lipoproteins, LDL / Q000276:immunology; D008315:Malondialdehyde / Q000031:analogs & derivatives / Q000276:immunology; D051379:Mice; D018384:Oxidative Stress / Q000276:immunology*
D000447:Aldehydes; D000939:Epitopes; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; C502964:malondialdehyde-low density lipoprotein, mouse; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal
Cell. 2008 Apr 18;133(2):235-49
18423196
J Clin Invest. 1996 Aug 1;98(3):800-14
8698873
Atherosclerosis. 2006 Nov;189(1):83-90
16386745
J Clin Invest. 2009 May;119(5):1335-49
19363291
Annu Rev Immunol. 2002;20:253-300
11861604
J Lipid Res. 2009 Apr;50 Suppl:S388-93
19106070
J Exp Med. 2004 Dec 6;200(11):1359-70
15583011
Arterioscler Thromb Vasc Biol. 2002 Jan;22(1):101-7
11788468
Nat Med. 2003 Jun;9(6):736-43
12740573
Autoimmunity. 2005 Jun;38(4):259-64
16206508
Circulation. 2009 Aug 4;120(5):417-26
19620499
Circulation. 2003 Oct 28;108(17):2107-12
14530200
J Lipid Res. 2005 Jul;46(7):1353-63
15897601
J Clin Invest. 2000 Jun;105(12):1731-40
10862788
Immunol Today. 1991 May;12(5):154-9
1715166
Trends Immunol. 2009 Jan;30(1):43-51
19058756
J Lipid Res. 2007 Feb;48(2):425-33
17093289
Springer Semin Immunopathol. 2005 Mar;26(4):347-62
15633017
Mol Immunol. 2000 Dec;37(18):1141-9
11451419
J Exp Med. 1982 Oct 1;156(4):1177-85
7153709
Nat Med. 2002 Nov;8(11):1218-26
12411948
Proc Natl Acad Sci U S A. 1999 May 25;96(11):6353-8
10339591
Arterioscler Thromb Vasc Biol. 2006 Sep;26(9):2096-102
16794225