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Blood, Vol. 95 No. 1 (January 1), 2000:
pp. 294-300
Viral latent membrane protein 1 (LMP-1)-induced CD99
down-regulation in B cells leads to the generation of cells with
Hodgkin's and Reed-Sternberg phenotype
Soon Ha Kim,
Young Kee Shin,
Im-soon Lee,
Young Mee Bae,
Hae Won Sohn,
Young Ho Suh,
Howe J. Ree,
Martin Rowe, and
Seong Hoe Park
From the Department of Pathology, Institute of Allergy and Clinical
Immunology, Seoul National University College of Medicine, Seoul,
Korea; DiNonA Inc, Suwon, Korea; the Department of Diagnostic
Pathology, Samsung Medical Center, Seoul, Korea; and the Department of
Medicine, University of Wales College of Medicine, Cardiff, UK.
Recently we reported that the down-regulation of CD99 (Mic2)
is a primary requirement for the generation of Hodgkin's and Reed-Sternberg (H-RS) cells seen in Hodgkin's disease. In
this study, we provide evidence that the down-regulation of CD99 is induced by high expression of Epstein-Barr virus (EBV) latent membrane
protein 1 (LMP-1), which is highly expressed in H-RS cells of
EBV-associated Hodgkin's disease. To investigate the effect of LMP-1
on the expression of CD99 in vitro, we established a stable cell line
by transfecting an SV40-early promoter driven-LMP-1 expression
construct into a neoplastic lymphoblastoid B cell line, IM9, in which
the level of endogenous LMP-1 expression is almost negligible. In this
cell line, the overexpression of LMP-1 led to the down-regulation of
CD99 and the acquisition of morphological and functional
characteristics of H-RS cells indistinguishable from those in lymph
nodes of Hodgkin's disease patients and in CD99-deficient B cells. In
addition, induced LMP-1 expression in an EBV-negative B cell clone,
BJAB, directly caused the down-regulation of surface CD99 expression.
Northern and Western analysis data, showing that overexpression of
LMP-1 negatively influenced the expression of CD99, were supported by
experiments in which a CD99 promoter-driven luciferase promoter
reporter construct transfected into 293T cells was down-regulated when
LMP-1 was coexpressed. Therefore, our data strongly suggest that the
EBV LMP-1 protein plays a pivotal role in the down-regulation of CD99
via transcriptional regulation, which leads to the generation of the
H-RS cells. (Blood. 2000;95:294-300)
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