Cultivated H-RS cells are resistant to CD95L-mediated apoptosis despite expression of wild-type CD95 (vol 28, pg 31, 2000)

Objective. In most cases of classic Hodgkin's disease (HD), Hodgkin and Ree d-Sternherg (H-RS) cells clonally derive from germinal-center B cells. With in their rearranged immunoglobulin genes, somatic mutations rendering poten tially functional immunoglobulin gene rearrangements nonfunctional were det ected, indicating that H-RS cells do not express a B-cell receptor. Under p hysiologic conditions, these cells would undergo apoptosis within the germi nal center. However, H-RS cells clonally expand, disseminate, and lead to c lonal relapse of HD, indicating their resistance to induced programmed cell death. The underlying mechanism remains to be elucidated. Materials and Methods. Analysis of receptor-ligand interactions in primary H-RS cells is difficult to perform due to their scarcity in vivo and their low proliferation rate in vitro. Therefore, two B-cellular H-RS cell lines (L1236 and L428) were used to test for the expression of CD95 by flow cytom etry and for the induction of apoptosis after incubation with CD95L obtaine d from retrovirally transduced murine myoblasts. Sequence analysis of CD95 cDNA obtained from these H-RS cell lines was performed. Results. Expression of CD95 on the cell surface was detected in both cell l ines. However, after incubation with CD95L, the cells did not undergo apopt osis, To test whether mutations within the CD95 cDNA sequence caused resist ance to apoptosis in H-RS cells, sequence analysis of CD95 cDNA obtained fr om L1236 and 1,428 was performed. In both cell lines, CD95 was not affected by somatic mutations. Conclusions. Our results indicate that the two H-RS cell lines (L1236 and L 428 are resistant to CD95-mediated apoptosis induced via CD95L, although wi ld-type CD95 is expressed. For further characterization of the mechanisms l eading to prevention of apoptotic cell death in H-RS cells, it is necessary to determine impairments within the signaling cascade following CD95 activ ation. (C) 2000 International Society for Experimental Hematology. Publishe d by Elsevier Science Inc.