Genetic analysis of indefinite division in human cells: evidence for a common immortalizing mechanism in T and B lymphoid cell lines.

Somatic cell hybrids are useful for gaining insight into the process(es) by which normal human cells undergo senescence. In previous studies, we found that hybrids generated by fusing normal human diploid fibroblasts, T lymphocytes, and endothelial cells with various immortal human cell lines exhibited limited division potential. This leads to the conclusion that the phenotype of cellular senescence is dominant and that immortal cells arise due to recessive changes in normal growth control mechanisms. Fusion of over 30 immortal cell lines led to the identification of four complementation groups for indefinite division. These data suggest that unlimited division potential can result from changes in at least four different genes or pathways. Complementation group assignment did not correlate with cell type, tumor type, embryonal layer of origin, or expression of an activated oncogene. The focus of this study was to determine the complementation group(s) to which various human lymphoblastoid cells assign so as to better understand the mechanism(s) by which these cell types undergo cellular senescence and immortalization. Seven lymphoid cell lines were studied and assigned to a single complementation group. This result supports the hypothesis that T and B cells undergo senescence by mechanisms similar to those occurring in fibroblasts and endothelial cells and provides evidence for a common mechanism(s) involving a senescence-related gene(s) for immortalization of these immune system derived cell lines.