Immortalized B lymphocytes produce B-cell growth factor

Abstract

The activation, clonal expansion and terminal differentiation of small resting B lymphocytes primed by an antigen (or antibodies to its receptors) appear to follow an orderly developmental sequence triggered at each stage by distinct soluble cytokines, primarily produced by T lymphocytes. For man, the only known B-cell mitogen independent of accessory cells for its action is the Epstein-Barr virus (EBV). Lymphocytes transformed by EBV are released from the usual constraints on B-cell growth, proliferating continuously in the absence of any exogenous cytokine. The resultant cell lines are of special interest as they possess certain features compatible with a preneoplastic state of Burkitt's lymphoma, one of two human cancers with which the virus is intimately associated. We report here that following EBV-transformation, B lymphoblasts release a soluble factor which mimics the B-cell stimulatory product(s) of mitogen-conditioned T lymphocytes. Furthermore, the virally-transformed cells utilize this activity to sustain their own growth. The ectopic production of an otherwise normal growth factor may represent a critical event in the malignant evolution of human lymphomas harbouring the EBV genome.