BAFF Receptor Deficiency Reduces the Development of Atherosclerosis in Mice-Brief Report
BAFF Receptor Deficiency Reduces the Development of Atherosclerosis in Mice-Brief Report
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DOI：
10.1161/atvbaha.111.244731
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发表时间：
2012-07-01
影响因子：
8.7
通讯作者：
Mallat, Ziad
中科院分区：
文献类型：
--
作者：
Sage, Andrew P.;Tsiantoulas, Dimitrios;Mallat, Ziad
目的 - 本研究的目的是评估 B 细胞激活因子 (BAFF) 受体在 B 细胞调节动脉粥样硬化中的作用。方法和结果 - 对雄性 LDL 受体缺陷型小鼠 (Ldlr(-/-)) 进行致死性照射，并用野生型或 BAFF 受体 (BAFF-R) 缺陷型骨髓进行重组。恢复 4 周后，小鼠接受高脂肪饮食 6 或 8 周。骨髓细胞中的 BAFF-R 缺陷导致传统成熟 B2 细胞显着减少，但不影响 B1a 细胞亚型。这与树突状细胞活化和 T 细胞增殖的显着减少以及针对丙二醛修饰的低密度脂蛋白的 IgG 抗体的减少有关。相反，血清IgM型抗体被保留。有趣的是，BAFF-R 缺陷与动脉粥样硬化病变发展的显着减少和斑块 T 细胞数量的减少有关。 B 细胞上的选择性 BAFF-R 缺陷会导致病变大小和 T 细胞浸润的类似减少，但相反不会影响树突状细胞活化。 结论：小鼠中 BAFF-R 缺陷选择性地改变成熟 B2 细胞依赖性细胞和体液免疫反应，并限制动脉粥样硬化的发展。 （动脉硬化血栓 Vasc Biol. 2012；32：1573-1576。）
Objective-The goal of this study was to assess the role of B-cell activating factor (BAFF) receptor in B-cell regulation of atherosclerosis.Methods and Results-Male LDL receptor-deficient mice (Ldlr(-/-)) were lethally irradiated and reconstituted with either wild type or BAFF receptor (BAFF-R)-deficient bone marrow. After 4 weeks of recovery, mice were put on a high-fat diet for 6 or 8 weeks. BAFF-R deficiency in bone marrow cells led to a marked reduction of conventional mature B2 cells but did not affect the B1a cell subtype. This was associated with a significant reduction of dendritic cell activation and T-cell proliferation along with a reduction of IgG antibodies against malondialdehyde-modified low-density lipoprotein. In contrast, serum IgM type antibodies were preserved. Interestingly, BAFF-R deficiency was associated with a significant reduction in atherosclerotic lesion development and reduced numbers of plaque T cells. Selective BAFF-R deficiency on B cells led to a similar reduction in lesion size and T-cell infiltration but in contrast did not affect dendritic cell activation.Conclusion-BAFF-R deficiency in mice selectively alters mature B2 cell-dependent cellular and humoral immune responses and limits the development of atherosclerosis. (Arterioscler Thromb Vasc Biol. 2012;32:1573-1576.)