Reversion of tumorigenicity in an EBV-converted Burkitt's lymphoma line.
One of five Epstein-Barr virus (EBV)-converted sublines of an EBV-negative Burkitt's lymphoma line (BL-41) was identified as a non-tumorigenic phenotypic revertant with low clonability, comparable to that of an EBV-transformed lymphoblastoid cell line (IARC-171) derived from the same patient. This revertant subline (BL-41/95) also showed the most LCL-like phenotype of the five convertants tested. It is suggested that reversion was due to the phenotypic shift of the cell from a 'window' of cell ontogeny that contains virgin B cells and memory B cells to the stage of the activated immunoblast. Constitutive activation of the c-myc gene by translocation to an immunoglobulin locus continues to drive proliferation of B cells in vivo even after they have undergone a programmed switch to a basically resting (virgin or memory cell) phenotype. An activated immunoblast invariably expresses c-myc. It is also suggested that proliferation of the activated immunoblast is regulated by negative host controls that prevent clonal overexpansion and keep the B cell pool constant. The sensitivity of the immunoblast to this control overrides the 'forward-driving' force of both EBV and the activated myc gene.
Klein
G
G
Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
D014408:Biomarkers, Tumor / Q000235:genetics; D002051:Burkitt Lymphoma / Q000209:etiology / Q000235:genetics*; D002999:Clone Cells; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007165:Immunosuppression Therapy; D010641:Phenotype; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor