Hodgkin's disease-derived cell lines--conflicting clues for the origin of Hodgkin's disease?

The origin of Hodgkin (H) and Reed-Sternberg (RS) cells remains a highly controversial issue. Studies on noncultured, freshly disaggregated biopsy material or of histological sections have not definitely established the cell lineage of HD cells, although evidence has been gathered that has allowed interpretation to favor one or the other hematopoietic cell type. In recent years a number of cell lines have been established from patients with Hodgkin's disease (HD) which are claimed to represent in vitro counterparts of H-RS cells. The phenotypic and functional properties of 7 HD-derived cell lines are reviewed here. The cell lines are not identical; they show many common features, but also a number of important differences in their phenotypes as well as in their in vitro behavior. The cell lines differ with some having characteristics of T cells, others of B cells, and yet others of the monocyte/macrophage cell lineage. This heterogeneity of H-RS established cell lines could be explained in a variety of ways: (a) the heterogeneity of HD itself might result from a disease process which leads to fusion of different cell types resulting in different phenotypic forms of H-RS cells depending on the cells involved; (b) the different cell types might reflect differences in the malignant cells present in the separate subtypes of HD; (c) the difficulty in successfully establishing H-RS cell lines might mean that unrepresentative cell types adapt to in vitro conditions. Rather than resolve the origin of H-RS cells, the established HD-derived cell lines have been consistent with the heterogeneity described in histochemical, immunohistological, and immunocytochemical studies.