Assessment Of Memory B Cells In Immune Disorders

一个开发记忆B细胞完整免疫表型的项目已经启动。这项工作正在评估正常受试者和患有特定免疫疾病（包括ALPS和CGD）的患者。此外，将免疫表型数据与P. Lipsky博士实验室（NIAMS）产生的单B细胞IG基因体细胞超突变结果进行比较。这些研究已经确定，CD27表达在CGD中改变，并且这似乎是缺陷氧化酶活性的直接产物，如通过CD27表达与X连锁携带者中正常细胞的比例之间的联系所反映的。此外，CD27表达在ALPS中显著减少，这可能在一定程度上与基于在ALPS患者血浆中发现的可溶性CD27水平增加的细胞表面的蛋白裂解有关。最近的研究结果表明，基于B细胞中正常的体细胞超突变频率，尽管B细胞上的CD 27表达显著降低，但CGD中的记忆B细胞水平是正常的。这与在ALPS患者的B细胞中使用相同的指示系统的记忆B细胞的实际缺乏以及在ALPS中减少的记忆B细胞中某些家族的过度表达形成对比，表明可能与在这种疾病中观察到的自身免疫相关的B细胞库偏斜。这些研究表明，Fas途径可能是关键的记忆B细胞的产生，而有缺陷的NADPH氧化酶活性不影响记忆B细胞的发展，但减少CD 27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。

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.