Suppression of malignancy in human lymphoid cell hybrids: The role of differentiation

Human somatic cell hybrids were generated from fusions between a tumorigenic B-cell line, and mononuclear cells from a patient with low-grade B-cell lymphoma in which the neoplastic cells largely corresponded to cells at an intermediate stage of differentiation. The resulting hybrids and the parent cells were immunophenotyped, karyotyped and genotyped in an effort to determine whether the stage of B-cell development of the fusion partners was important in the suppression of malignancy. The majority of hybrids demonstrated suppression of tumorigenicity as measured in immunodeprived mice. Chromosome markers and immunoglobulin gene rearrangements found in the patient’s neoplastic cells were also present in several of the hybrids. One of the tumorigenic hybrids retained specific chromosomes also found in the non-tumorigenic hybrids, but demonstrated an immunophenotype and genotype possibly associated with a subset of early B-cells. In the non-tumorigenic hybrids that retained most of the chromosomes from both parents there was evidence of plasmacytoid differentiation. These results suggest that the ability of B-lymphocytes to suppress malignancy in human lymphoid hybrids may be dependent on the corresponding stage of normal B-cell ontogeny, and that suppression is associated with differentiation.