Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity
Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity
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DOI：
10.1172/jci8472
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发表时间：
2000-06-01
影响因子：
15.9
通讯作者：
Witztum, JL
中科院分区：
文献类型：
--
作者：
Shaw, PX;Hörkkö, S;Witztum, JL
对氧化型低密度脂蛋白（OxLDL）的免疫应答可能在动脉粥样硬化的形成中起重要作用。使用apoE缺陷小鼠，我分离出一组oxLDL特异性B细胞系，其分泌特异性结合氧化磷脂如1-棕榈酰-2-（5-氧代戊酰基）-sn-甘油基-3-磷酸胆碱（POVPC）的IgM Ab。这些抗体阻断巨噬细胞对OxLDL的摄取，识别凋亡细胞上类似的氧化特异性表位，并沉积在动脉粥样硬化病变中。发现Ab在结构上和功能上与经典的“天然”T15抗PC Ab相同，所述T15抗PC Ab是B-1细胞来源的，并且据报道提供最佳保护以免受毒性肺炎球菌感染。这些发现表明，分泌氧化特异性/T15抗体的B-1细胞存在自然选择，因为它们在自然免疫防御中的作用以及在健康和疾病中对氧化依赖性新决定因素的管家作用。
The immune response to oxidized LDL (OxLDL) may play an important role in atherogenesis. Working with apoE-deficient mice, me 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.