Carbone A, Gloghini A, Gaidano G, Franceschi S, Capello D, Drexler H G, Falini B, Dalla-Favera R
Division of Pathology, Centro di Riferimento Oncologico, IRCCS, Istituto Nazionale Tumori, Aviano, Italy.
Blood. 1998 Oct 1;92(7):2220-8.
The tumor cells in most cases of Hodgkin's disease (HD) have been recently recognized to originate from the B-cell lineage, but their precise differentiation stage is not fully clarified. Recently, we have reported that the histogenesis of B-cell lymphomas may be assessed by monitoring the expression pattern of BCL-6, a transcription factor expressed in germinal center (GC) B cells, and CD138/syndecan-1 (syn-1), a proteoglycan associated with post-GC, terminal B-cell differentiation. In this study, we have applied these two markers to the study of HD histogenesis. We have found that in nodular lymphocyte predominance HD (NLPHD) tumor cells consistently display the BCL-6(+)/syn-1(-) phenotype, indicating their derivation from GC B cells. Conversely, classic HD (CHD) is heterogeneous because the tumor cells of a fraction of CHD display the BCL-6(-)/syn-1(+) phenotype of post-GC B-cells, whereas another fraction of CHD is constituted by a mixture of tumor cells reflecting the GC (BCL-6(+)/syn-1(-)) or post-GC (BCL-6(-)/syn-1(+)) phenotypes. BCL-6(-)/syn-1(+) tumor cells of CHD are mostly found surrounded by T cells expressing CD40L, consistent with the observation that CD40 signaling downregulates BCL-6 expression. These data indicate that tumor cells of NLPHD uniformly display a GC B-cell phenotype, whereas the phenotype of tumor cells of CHD appears to be modulated by the surrounding cellular background, particularly CD40L+ reactive T cells.
最近人们认识到，大多数霍奇金淋巴瘤（HD）病例中的肿瘤细胞起源于B细胞谱系，但其确切的分化阶段尚未完全阐明。最近，我们报道了B细胞淋巴瘤的组织发生可以通过监测BCL-6的表达模式来评估，BCL-6是一种在生发中心（GC）B细胞中表达的转录因子，以及CD138/多配体聚糖-1（syn-1），一种与GC后终末B细胞分化相关的蛋白聚糖。在本研究中，我们将这两种标志物应用于HD组织发生的研究。我们发现，在结节性淋巴细胞为主型HD（NLPHD）中，肿瘤细胞始终表现为BCL-6(+)/syn-1(-)表型，表明它们来源于GC B细胞。相反，经典HD（CHD）是异质性的，因为一部分CHD的肿瘤细胞表现为GC后B细胞的BCL-6(-)/syn-1(+)表型，而另一部分CHD则由反映GC（BCL-6(+)/syn-1(-)）或GC后（BCL-6(-)/syn-1(+)）表型的肿瘤细胞混合物组成。CHD的BCL-6(-)/syn-1(+)肿瘤细胞大多被表达CD40L的T细胞包围，这与CD40信号下调BCL-6表达的观察结果一致。这些数据表明，NLPHD的肿瘤细胞一致表现为GC B细胞表型，而CHD肿瘤细胞的表型似乎受到周围细胞背景的调节，特别是CD40L+反应性T细胞。
