B-1b Cells Secrete Atheroprotective IgM and Attenuate Atherosclerosis. Issue 3 (17th July 2015)

• Record Type: Journal Article
• Authors: Rosenfeld, Sam M.; Perry, Heather M.; Gonen, Ayelet; Prohaska, Thomas A.; Srikakulapu, Prasad; Grewal, Sukhdeep; Das, Deepanjana; McSkimming, Chantel; Taylor, Angela M.; Tsimikas, Sotirios; Bender, Timothy P.; Witztum, Joseph L.; McNamara, Coleen A.
• Is Part Of: Circulation research. Volume 117:Issue 3(2015)
• Publication Date: 2015-07-17
• Subjects: Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.117.306044
• Languages: English
• ISSNs: 0009-7330

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title> <underline>Rationale:</underline> </title> <p>B cells contribute to atherosclerosis through subset-specific mechanisms. Whereas some controversy exists about the role of B-2 cells, B-1a cells are atheroprotective because of secretion of atheroprotective IgM antibodies independent of antigen. B-1b cells, a unique subset of B-1 cells that respond specifically to T-cell–independent antigens, have not been studied within the context of atherosclerosis.</p> </sec> <sec> <title> <underline>Objective:</underline> </title> <p>To determine whether B-1b cells produce atheroprotective IgM antibodies and function to protect against diet-induced atherosclerosis.</p> </sec> <sec> <title> <underline>Methods and Results:</underline> </title> <p>We demonstrate that B-1b cells are sufficient to produce IgM antibodies against oxidation-specific epitopes on low-density lipoprotein both in vitro and in vivo. In addition, we demonstrate that B-1b cells provide atheroprotection after adoptive transfer into B- and T-cell deficient (<italic>Rag1</italic><sup>−/−</sup><italic>Apoe</italic><sup>−/−</sup>) hosts. We implicate inhibitor of differentiation 3 (Id3) in the regulation of B-1b cells as B-cell–specific Id3 knockout mice (Id3<sup>BKO</sup><italic>Apoe</italic><sup>−/−</sup>) have increased numbers of B-1b cells systemically, increased titers of oxidation-specific epitope–reactive IgM antibodies, and significantly reduced diet-induced atherosclerosis when compared with Id3<sup>WT</sup><italic>Apoe</italic><sup>−/−</sup> controls. Finally, we report that the presence of a homozygous single nucleotide polymorphism in <italic>ID3</italic> in humans that attenuates Id3 function is associated with an increased percentage of circulating B-1 cells and anti–malondialdehyde-low-density lipoprotein IgM suggesting clinical relevance.</p> </sec> <sec> <title> <underline>Conclusions:</underline> </title> <p>These results provide novel evidence that B-1b cells produce atheroprotective oxidation-specific epitope–reactive IgM antibodies and protect against atherosclerosis in mice and suggest that similar mechanisms may occur in humans.</p> </sec> </abstract>