GENERATION OF CELLS WITH HODGKINS AND REED-STERNBERG PHENOTYPE THROUGH DOWN-REGULATION OF CD99 (MIC2)

Despite the fact that Hodgkin's and Reed-Sternberg (H-RS) cells are mo rphological hallmarks of Hodgkin's disease (HD), the nature of H-RS ce lls still remains to be resolved. Here we report that downregulation o f 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 CD9 9 expression construct showed the morphological and immunological char acteristics 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 expr ession of CD99 was also confirmed in H-RS cells of patient's lymph nod es and three HD-derived cell lines, L428, KM-HP, and HDLM-2. Moreover, features characteristic of H-RS cells were completely abolished by fo rced expression of CD99 and by a constitutively active form of pac, wh ich 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. (C) 1998 by The A merican Society of Hematology.