Assessment Of Memory B Cells In Immune Disorders

一个开发记忆B细胞完全免疫表型的项目已经启动。这是评估正常受试者和特异性免疫疾病患者，包括ALPS和CGD。此外，免疫表型数据正在与P. Lipsky博士实验室（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表达在CGD中发生改变，这似乎是氧化酶活性缺陷的直接产物，正如CD27表达与x连锁携带者中正常细胞比例之间的联系所反映的那样。此外，CD27在ALPS中的表达明显减少，这可能与基于在ALPS患者血浆中发现的可溶性CD27水平升高的细胞表面蛋白切割有关。最近的研究结果表明，基于B细胞体细胞超突变的正常频率，CGD患者的记忆B细胞水平是正常的，尽管B细胞上CD27的表达明显降低。这与阿尔卑斯山患者B细胞中使用相同指示系统的记忆性B细胞的缺失形成对比，并且在阿尔卑斯山记忆性B细胞减少中某些家族的过度表达表明B细胞库倾斜可能与该疾病中所见的自身免疫有关。这些研究表明，Fas通路可能在记忆性B细胞的产生中起关键作用，而NADPH氧化酶活性缺陷不影响记忆性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细胞的一贯可靠标记。

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.