ABSENCE OF T-CELL-SPECIFIC AND B-CELL-SPECIFIC TRANSCRIPTION FACTORS TCF-1, GATA-3, AND BSAP IN HODGKINS REED-STERNBERG CELLS

Based on the presence of T cell receptor-beta (TcR-beta) gene rearrang ements in L428 and HDLM-1 cells, the expression of CD2 in HDLM-1 cells , and the presence of immunoglobulin heavy-chain (IgH) gene rearrangem ent in KM-H2 cells, some researchers have concluded that these long-te rm cell lines derived from patients with Hodgkin's disease are lymphoi d in nature. The information obtained from these cell lines has also b een used in arguments for a lymphoid origin of H-RS cells in tissue de spite the frequent absence of lymphoid markers and Ig/TcR gene rearran gements in these cells. We questioned whether one can use the limited expression of lymphoid markers or the limited gene rearrangement to co nclude that H-RS cells have a lymphoid origin, because these markers m ay be aberrant in tumor cells. In this study, we examined the expressi on of two T-cell-specific transcription factors (TCF-1 and GATA-3) and one B-cell-specific transcription factor (BSAP) in cultured H-RS cell s by using a gel mobility shift assay. The sensitivity and specificity of this assay for determination of cell lineage have been established in a large number of cultured human and murine cell lines. All three types of H-RS cell lines were consistently negative for BSAP, TCF-1, a nd GATA-3. The absence of GATA-3 was confirmed in H-RS cells in tissue s by an in situ hybridization technique. Virtually all B-cell lines, w ith the exception of some myeloma cell lines, are positive for BSAP, w hich is the transcription factor for promoters for several B-cell mark ers, including V-preB1, lambda 5, CD19, and CD20. All T-cell lines tes ted were positive for TCF-1 and GATA-3, which are the transcription fa ctors for promoters for several T-cell-restricted markers, including C D2, CD3, TcR, and Ick. The absence of BSAP, TCF-1, and GATA-3 clearly indicates an underlying difference between H-RS cells and lymphoid cel ls.