Self-stimulating growth factor production by B-cell lines derived from Burkitt's lymphomas and other lines transformed in vitro by Epstein-Barr virus

Abstract

Kinetics of cell growth of human B-lymphocyte lines derived from Burkitt's lymphomas and lines derived from the Epstein-Barr virus transformation of normal adult lymphocytes were studied. Cells seeded at high densities (5 X 10(4)/ml) grew in an exponential manner; those seeded at low densities (5 X 10(3) to 1 X 10(4) began to grow exponentially only after a lag period of 3 to 4 days. Transfer of stationary low-density cell populations into filtered media from growing high-density cultures (conditioned media) stimulated cell growth, as determined both by increased cell numbers and [3H]thymidine incorporation. Enhanced cell growth occurred in conditioned media at all cell seeding concentrations that grew in normal media. Furthermore, cultures seeded at very low cell concentrations that do not grow in normal media proliferated in conditioned media. Media from a series of B-cell lines tested with one exception were autostimulatory. Reciprocal cell transfer experiments showed that media from B-cell lines cross-stimulated cells in other B-cell lines. Media from the non-B-cell lines tested were not autostimulatory and did not stimulate growth of the B-cell lines, and conversely these non-B-cell lines were not growth enhanced by the conditioned media. Absorption of growth-enhancing media with preincubated cell lines seeded at low density removed the enhancing capacity. These results demonstrate that B-cell lines from Burkitt's lymphomas and B-cells transformed in vitro by Epstein-Barr virus produce absorbable growth-enhancing factor(s) that may be essential to the development of perpetual growth in culture.