Falini B, Bigerna B, Pasqualucci L, Fizzotti M, Martelli M F, Pileri S, Pinto A, Carbone A, Venturi S, Pacini R, Cattoretti G, Pescarmona E, Lo Coco F, Pelicci P G, Anagnastopoulos I, Dalla-Favera R, Flenghi L
Institute of Hematology, University of Perugia, Italy.
Blood. 1996 Jan 15;87(2):465-71.
The BCL-6 gene encoding a nuclear-located Kruppel-type zinc finger protein is rearranged in about 30% diffuse large B-cell lymphomas and is expressed predominantly in normal germinal center B cells and related lymphomas. These findings suggest that BCL-6 may play a role in regulating differentiation of normal germinal center B cells and that its deregulated expression caused by rearrangements may contribute to lymphomagenesis. This prompted us to investigate the expression of the BCL-6 protein in Hodgkin's disease (HD), focusing on the nodular lymphocyte predominance subtype (NLPHD), which differs from classical HD by virtue of the B-cell nature of the malignant cell population (so-called L&H cells) and its relationship with germinal centers. Forty-one HD samples (19 NLPHD, 12 nodular sclerosis, and 10 mixed cellularity) were immunostained with the monoclonal antibodies PG-B6 and PG-B6p that react with a fixative-sensitive and a formalin-resistant epitope on the aminoterminal region of the BCL-6 gene product, respectively. Strong nuclear positivity for the BCL-6 protein was detected in tumor (L&H) cells in all cases of NLPHD. In contrast, BCL-6 was expressed only in a small percentage of Hodgkin and Reed-Sternberg cells in about 30% of classical HD cases. Notably, the nuclei of reactive CD3+/CD4+ T cells nearby to and rosetting around L&H cells in NLPHD were also strongly BCL-6+, but lacked CD40 ligand (CD40L) expression. This staining pattern clearly differed from that of classical HD, whose cellular background was made up of CD3+/CD4+ T cells showing the BCL-6-/CD40L+ phenotype. These results further support the concept that NLPHD is an histogenetically distinct, B-cell-derived subtype of HD and suggest a role for BCL-6 in its development.
编码一种位于细胞核的克鲁ppel型锌指蛋白的BCL-6基因，在大约30%的弥漫性大B细胞淋巴瘤中发生重排，并且主要在正常生发中心B细胞及相关淋巴瘤中表达。这些发现提示，BCL-6可能在调节正常生发中心B细胞的分化中发挥作用，并且其因重排导致的表达失调可能促成淋巴瘤的发生。这促使我们研究霍奇金淋巴瘤（HD）中BCL-6蛋白的表达，重点关注结节性淋巴细胞为主型亚型（NLPHD），该亚型与经典HD不同，因其恶性细胞群体（所谓的L&H细胞）的B细胞性质及其与生发中心的关系。41例HD样本（19例NLPHD、12例结节硬化型和10例混合细胞型）用单克隆抗体PG-B6和PG-B6p进行免疫染色，这两种抗体分别与BCL-6基因产物氨基末端区域的一种对固定剂敏感的表位和一种抗福尔马林表位发生反应。在所有NLPHD病例的肿瘤（L&H）细胞中均检测到BCL-6蛋白强核阳性。相比之下，在约30%的经典HD病例中，BCL-6仅在一小部分霍奇金和里德-斯腾伯格细胞中表达。值得注意的是，NLPHD中靠近L&H细胞并与其形成花结的反应性CD3+/CD4+ T细胞核也呈BCL-6强阳性，但缺乏CD40配体（CD40L）表达。这种染色模式与经典HD明显不同，经典HD的细胞背景由显示BCL-6-/CD40L+表型的CD3+/CD4+ T细胞组成。这些结果进一步支持了NLPHD是HD的一种组织发生学上不同的、B细胞来源的亚型这一概念，并提示BCL-6在其发生发展中起作用。
