Core B: Immunoassay Core

核心B项目摘要 Core B将与这四个项目中的每一个项目合作，在小鼠和人类身上提供相关的免疫分析： 与Hedrick博士合作的项目1将使用小鼠模型来测试新的单核细胞亚群的影响 调节动脉壁中T细胞和B细胞的反应，对动脉粥样硬化和先天免疫的影响。核心将能够 检测氧化特异性表位(OSE)和载脂蛋白B免疫复合体的自身抗体 以及血浆总免疫球蛋白和免疫球蛋白M水平，以评估这些单核细胞亚群的影响以及与 在这些测量上的淋巴细胞。然后可以根据B1和B2细胞功能从 麦克纳马拉博士的项目也与莱伊博士实验中单核细胞细胞因子的释放有关。 与米勒博士合作的项目2将使用核心来测量个体上的氧化胆固醇酯 脂蛋白，这是我们的实验室与米勒博士共同开发的一种分析方法， 他的部分提供了临床数据。我们已经建立的临床检测，如OxPL-apoB，Lp(A)， 还将检测免疫球蛋白G和免疫球蛋白M自身抗体以及载脂蛋白B免疫复合体。这些措施可以 然后与冠状动脉钙化(CAC)的存在和程度以及进展有关 CAC及其与心血管事件的关系。此外，它们还可以与AIBP水平和 从各种实验中得到了高密度脂蛋白参数。 与麦克纳马拉博士合作的项目3将评估调节它们生产能力的机制 抗动脉粥样硬化部分，如免疫球蛋白M到OSE。该项目预计将在B1中生成重要数据 小鼠模型中的生物学研究，所有这些都将与测定免疫球蛋白抗体和免疫球蛋白M自身抗体效价高度相关。我们 也有能力在我们这样的小鼠中检测到动脉粥样硬化保护性抗体E06的存在 获得E06、AB1-2的抗独特型抗体。最后，测量免疫球蛋白抗体和免疫球蛋白M抗体的总水平是 口译实验研究的一个重要方面，这也将被测量。这样的化验是 目前可用，之前已在与McNamara博士的合作中描述和发表 与莱伊博士合作的项目4将确定小鼠体内ApoB特异性CD4T细胞的大小和性质。这个 小鼠载脂蛋白B免疫复合物抗体LF3捕获小鼠载脂蛋白B 然后评估载脂蛋白B结合抗体的存在。这些化验结果将与此高度相关 解释这些小鼠中是否产生了含有小鼠载脂蛋白B的免疫复合体。 此外，我们还可以用这些方法检测小鼠的总载脂蛋白B水平作为对照措施。

Core B Project Summary Core B will work with each of the four projects to provide relevant immunoassays in mice and in humans: Project 1 with Dr Hedrick will use mouse models to test the impact of new monocyte subsets that regulate T and B cell responses in the artery wall, on atherogenesis and innate immunity. The Core will be able to measure IgG and IgM autoantibodies to oxidation-specific epitopes (OSE) and ApoB-immune complexes, as well as total IgG and IgM plasma levels to assess the impact of these monocyte subsets and interaction with lymphocytes on these measurements. These can then be analyzed according to B1 and B2 cell function from Dr. McNamara's projects and to also correlate with monocyte cytokine release from Dr. Ley's experiments. Project 2 with Dr. Miller will use the Core to measure oxidized cholesteryl esters on individual lipoproteins, an assay that has been co-developed by our laboratory with Dr. Miller and for which preliminary clinical data is provided in his section. Clinical assays that we have established, such as OxPL-apoB, Lp(a), and IgG and IgM autoantibodies and ApoB-immune complexes will also be measured. These measures can then be related to both the presence and extent of coronary artery calcium (CAC), as well as the progression of CAC and the relationship with cardiovascular events. Furthermore, they can be correlated with AIBP levels and HDL parameters from the various experiments. Project 3 with Dr McNamara will evaluate the mechanism that regulates their ability to produce atheroprotective moieties such as IgM to OSE. This project is expected to generate significant data in B1 biology in mouse models, all of which will be highly relevant to measuring IgG and IgM autoantibody titers. We also have the ability to measure the presence of the atheroprotective antibody E06 in such mice as we have access to an anti-idiotype antibody to E06, AB1-2. Finally, measuring total levels of IgG and IgM antibodies is an important aspect in interpreting experimental studies, which will also be measured. Such assays are currently available and have been previously described and published in collaborative work with Dr. McNamara Project 4 with Dr. Ley will define the size and nature of the ApoB-specific CD4 T cell in mice. The mouse apoB-immune complex assays capture murine apoB using murine monoclonal antibody antibody LF3 and then assess the presence of a bound antibody to the apoB. These assays will be highly relevant to this work in interpreting whether immune complexes containing murine apoB are generated in these mice. Furthermore, we can measure murine total apoB levels with these assays as a control measure.