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Blood, Vol. 96 No. 1 (July 1), 2000:
pp. 224-233
CD9 expression enhances the susceptibility of myeloma cell
lines to cell-mediated cytolysis
Suhair Shallal and
Jacki Kornbluth
From the Department of Microbiology and Immunology, University of
Arkansas for Medical Sciences, Little Rock, and the Department of
Pathology, St Louis University School of Medicine, St Louis, MO.
Myeloma tumor cells, both freshly excised and cultured, are
extremely resistant to cell-mediated cytolysis. As evidence suggests that B-cell susceptibility to lysis is dependent upon its state of
differentiation and activation, we tested the ability of a variety of
B-cell proliferation and differentiation agents, including pokeweed
mitogen (PWM), to enhance the sensitivity of myeloma cells to
cell-mediated lysis. PWM was found to significantly enhance the
susceptibility of myeloma cell lines and freshly isolated myeloma cells
to interleukin-2 (IL-2)-activated cell-mediated cytolysis. This effect
was seen with the use of both IL-2-stimulated natural killer (NK)
cells and T cells as effectors. The enhanced sensitivity of myeloma
cells to cytolysis correlated with an increase in their cell surface
expression of CD9, a pre-B cell marker and member of the transmembrane
4 superfamily. Incubation of PWM-stimulated myeloma cells with either
monoclonal antibodies or antisense oligonucleotides directed against
CD9 abrogated the effect of PWM. In order to determine whether there
was a direct relationship between the expression of CD9 and enhanced
sensitivity to cytolysis, myeloma cell lines that lacked CD9
expression were transfected with the CD9 gene. The level
of cell surface CD9 expression correlates with enhanced susceptibility
to lysis. Therefore, CD9 appears to be an important component in
enhancing the sensitivity of myeloma cells to lysis mediated by
IL-2-activated T cells and NK cells.
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