Assessment Of Memory B Cells In Immune Disorders

免疫疾病中记忆 B 细胞的评估

• 批准号: 6825555
• 负责人: thomas a fleisher
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6825555
• 关键词: B lymphocyte; CD antigens; cell population study; chronic granulomatous disease; clinical research; disease /disorder etiology; gene expression; genetic regulation; human subject; immunogenetics; immunoglobulin genes; immunopathology; immunoregulation; molecular pathology; oxidoreductase; protein structure function

A project to develop the complete immunophenotype of memory B cell has been initiated. This is being done evaluating normal subjects and patients with specific immune disorders including ALPS and CGD. In addition, the immunophenotypic data is being compared with single B cell Ig gene somatic hypermutation results generated in Dr. P. Lipsky's laboratory (NIAMS). These investigations have established that CD27 expression is altered in CGD and this appears to be a direct product of the defective oxidase activity as reflected by the link between CD27 expression and the proportion of normal cells in X-linked carriers. In addition, CD27 expression is markedly diminished in ALPS that may be related to some extent to protein cleavage from the cell surface based on increased levels of soluble CD27 found in the plasma of ALPS patients. Recent findings suggest that memory B cell levels are normal in CGD based on normal frequency of somatic hypermutation in B cells despite the marked decrease in CD27 expression on the B cells. This contrasts with a virtual absence of memory B cells using the same indicator system in ALPS patient's B cells and the over expression of certain families among the diminished memory B cells in ALPS suggesting B cell repertoire skewing that may be associated with the autoimmunity seen in this disorder. These studies suggest that the Fas pathway may be critical in the generation of memory B cells while defective NADPH oxidase activity does not impact memory B cell development but does diminish CD27 expression. These studies also point out the CD27 is not a consistently reliable marker of memory B cells in humans.

一个开发记忆B细胞的完整免疫表型的项目已经启动。这项研究正在评估正常受试者和患有特殊免疫疾病的患者，包括阿尔卑斯病和慢性粒细胞增多症。此外，免疫表型数据正在与P.Lipsky博士的实验室(NIAMS)产生的单个B细胞Ig基因体细胞超突变结果进行比较。这些研究已经证实，CD27在CGD中的表达发生了改变，这似乎是氧化酶活性缺陷的直接产物，这一点从CD27表达与X连锁携带者中正常细胞比例之间的联系中得到了反映。此外，阿尔卑斯病患者血浆中可溶性CD27水平升高，CD27表达明显降低，这可能在一定程度上与蛋白质从细胞表面切割有关。最近的研究结果表明，尽管CD27在B细胞上的表达显著降低，但CGD患者的记忆B细胞水平是正常的，这是基于B细胞体细胞过度突变的正常频率。这与阿尔卑斯山患者B细胞中使用相同指示系统的记忆B细胞几乎不存在，以及阿尔卑斯山患者记忆B细胞中某些家族的过度表达形成对比，这表明B细胞谱系的扭曲可能与这种疾病中的自身免疫有关。这些研究表明，Fas途径可能在记忆B细胞的产生中起关键作用，而NADPH氧化酶活性缺陷不会影响记忆B细胞的发育，但会减少CD27的表达。这些研究还指出，CD27并不是人类记忆B细胞的可靠标记。