Buettner Maike, Greiner Axel, Avramidou Athanasia, Jäck Hans-Martin, Niedobitek Gerald
Institute for Pathology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center, Friedrich-Alexander-University, Erlangen, Germany.
Hematol Oncol. 2005 Sep-Dec;23(3-4):127-32. doi: 10.1002/hon.764.
Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) show genotypic features of germinal centre-derived B-cells in most cases. Nevertheless, these cells typically lack expression of B-cell antigens. Previous studies have suggested that plasma cell differentiation may occur in HRS cells and that this may account for the down-regulation of B-cell antigens. However, these results are controversial. We have addressed this question using immunohistochemistry and a panel of antibodies directed against antigens which are differentially expressed during terminal B-cell differentiation. Pax-5, a transcription factor required for B-lineage commitment, and IRF4/Mum1, which is physiologically expressed in germinal centre cells and plasma cells, were consistently detectable in HRS cells. Bcl-6, a transcription factor expressed in germinal centre B-cells, was present in HRS cells of approximately 25% of cHL cases. Expression of the B-lymphocyte-induced maturation protein-1 (Blimp-1), a key regulator of plasma cell differentiation, was observed in HRS cells of 23% of cHL cases. In these cases, Blimp-1 expression was restricted to a small proportion of HRS cells. HRS cells were consistently negative for the plasma cell marker CD138. These results suggest that plasma cell differentiation may be initiated in a small subset of HRS cells but remains abortive. Thus, terminal differentiation is unlikely to explain the lack of B-cell antigen expression in HRS cells.
在大多数情况下，经典型霍奇金淋巴瘤（cHL）的霍奇金和里德-斯腾伯格（HRS）细胞显示出源自生发中心的B细胞的基因型特征。然而，这些细胞通常缺乏B细胞抗原的表达。先前的研究表明，HRS细胞中可能发生浆细胞分化，这可能是B细胞抗原下调的原因。然而，这些结果存在争议。我们使用免疫组织化学和一组针对在B细胞终末分化过程中差异表达的抗原的抗体来解决这个问题。Pax-5是B细胞谱系定向所需的转录因子，IRF4/Mum1在生发中心细胞和浆细胞中生理性表达，在HRS细胞中始终可检测到。Bcl-6是一种在生发中心B细胞中表达的转录因子，在约25%的cHL病例的HRS细胞中存在。在23%的cHL病例的HRS细胞中观察到浆细胞分化的关键调节因子B淋巴细胞诱导成熟蛋白-1（Blimp-1）的表达。在这些病例中，Blimp-1的表达仅限于一小部分HRS细胞。HRS细胞对浆细胞标志物CD138始终呈阴性。这些结果表明，浆细胞分化可能在一小部分HRS细胞中启动，但仍未完成。因此，终末分化不太可能解释HRS细胞中B细胞抗原表达的缺乏。
