Academic Journal
B-1b Cells Secrete Atheroprotective IgM and Attenuate Atherosclerosis
| العنوان: | B-1b Cells Secrete Atheroprotective IgM and Attenuate Atherosclerosis |
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| المؤلفون: | 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. |
| المصدر: | Circulation Research ; volume 117, issue 3 ; ISSN 0009-7330 1524-4571 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health) |
| سنة النشر: | 2015 |
| الوصف: | Rationale: 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. Objective: To determine whether B-1b cells produce atheroprotective IgM antibodies and function to protect against diet-induced atherosclerosis. Methods and Results: 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 ( Rag1 −/− Apoe −/− ) hosts. We implicate inhibitor of differentiation 3 (Id3) in the regulation of B-1b cells as B-cell–specific Id3 knockout mice (Id3 BKO Apoe −/− ) 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 WT Apoe −/− controls. Finally, we report that the presence of a homozygous single nucleotide polymorphism in ID3 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. Conclusions: 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1161/circresaha.117.306044 |
| DOI: | 10.1161/CIRCRESAHA.117.306044 |
| الاتاحة: | http://dx.doi.org/10.1161/circresaha.117.306044 https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.117.306044 |
| رقم الانضمام: | edsbas.879CEFB4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1161/circresaha.117.306044 |
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