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Blood, Vol. 92 No. 11 (December 1), 1998:
pp. 4287-4295
Generation of Cells With Hodgkin's and Reed-Sternberg Phenotype
Through Downregulation of CD99 (Mic2)
Soon Ha Kim,
Eun Young Choi,
Young Kee Shin,
Tae Jin Kim,
Doo Hyun Chung,
Sung Ik Chang,
Noe Kyeong Kim, and
Seong Hoe Park
From the Departments of Pathology and Internal Medicine, Seoul
National University College of Medicine, Seoul, Korea; the Department
of Pathology, Sungkyunkwan University College of Medicine, Suwon,
Korea; and the Department of Anatomy and Medical Genetics, Keimyung
University, School of Medicine, Taegu, Korea.
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.
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