Growth of E mu-myc transgenic B-lymphoid cells in vitro and their evolution toward autonomy

Constitutive expression of the c-myc oncogene in the B lymphoid cells of E mu-myc transgenic mice promotes cellular proliferation and predisposes to lymphomagenesis. To delineate further how the pre-B cells of prelymphomatous mice have been altered, we have investigated their growth in vitro. They were not autonomous, since they died rapidly when cultured without feeder cells. When cultured on bone marrow stromal cells, E mu-myc cells initially grew to only slightly higher densities than B lineage cells from normal mice, but were larger and showed more cell cycle activity. After 14 weeks, all cultures appeared oligo- or monoclonal, as judged by analysis of Ig gene rearrangements. While the growth of the normal cells was constant, the E mu-myc cells started to grow to 10-fold higher densities after 14-20 weeks, implying a reduced requirement for growth factors. They remained dependent on feeder cells and were non-tumorigenic. By 25 weeks, however, the one remaining culture had become feeder-independent and tumorigenic. We suggest that deregulated c-myc expression in B cell precursors increases the rate of cell turnover, thereby increasing the frequency of genetic changes conductive to autonomous growth.