Kim S H, Choi E Y, Shin Y K, Kim T J, Chung D H, Chang S I, Kim N K, Park S H
Departments of Pathology and Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Blood. 1998 Dec 1;92(11):4287-95.
Despite the fact that Hodgkin's and Reed-Sternberg (H-RS) cells are morphological hallmarks of Hodgkin's disease (HD), the nature of H-RS cells still remains to be resolved. Here we report that downregulation of CD99 (Mic2) leads to the generation of cells with an H-RS phenotype. IM9 and BJAB B-cell lines that were transfected with an antisense CD99 expression construct showed the morphological and immunological characteristics of H-RS cells such as multinuclearity, expression of CD15, decreased expression of major histocompatibility complex (MHC) class I and CD45RB, and deregulated secretion of cytokines. The reduced expression of CD99 was also confirmed in H-RS cells of patient's lymph nodes and three HD-derived cell lines, L428, KM-H2, and HDLM-2. Moreover, features characteristic of H-RS cells were completely abolished by forced expression of CD99 and by a constitutively active form of Rac, which functions downstream of CD99. We suggest that CD99 molecules play a crucial role in regulating functions and morphology of cells through a Rac-Rho signaling pathway and that the loss of CD99 expression is a significant molecular event to generate H-RS cells.
尽管霍奇金和里德-斯腾伯格（H-RS）细胞是霍奇金淋巴瘤（HD）的形态学标志，但H-RS细胞的本质仍有待阐明。在此我们报告，CD99（Mic2）的下调导致具有H-RS表型的细胞产生。用反义CD99表达构建体转染的IM9和BJAB B细胞系表现出H-RS细胞的形态学和免疫学特征，如多核性、CD15表达、主要组织相容性复合体（MHC）I类和CD45RB表达降低以及细胞因子分泌失调。患者淋巴结的H-RS细胞以及三个HD来源的细胞系L428、KM-H2和HDLM-2中也证实了CD99表达降低。此外，通过强制表达CD99和通过在CD99下游起作用的组成型活性形式的Rac，H-RS细胞的特征完全消失。我们认为，CD99分子通过Rac-Rho信号通路在调节细胞功能和形态方面起关键作用，并且CD99表达的丧失是产生H-RS细胞的一个重要分子事件。
