Stage-specific transformation of murine B lineage cells by ras and myc.

The retroviral vector delta RM coexpresses the v-Ha-ras and v-mycMC29 oncogenes, under the transcriptional control of the retroviral long terminal repeat and an internal SV40 promoter respectively. In this report, the transforming activity of the delta RM virus on murine pre-B cells has been compared and contrasted with its activity on mature splenic B cells. Infection of primary bone marrow cells, followed by growth in the Whitlock-Witte culture system, resulted in the rapid outgrowth of transformed pre-B cells. These cells grew to high saturation densities and could give rise to immortal, interleukin-7-independent progeny that were able to grow independently of stromal elements. In contrast, infection of mature B cells purified from murine spleen resulted in only a transient increase in proliferation, and no immortal B cell lines were obtained. This inability of delta RM to transform mature B lymphocytes was not due to a low infection frequency, since parallel experiments with ecotropic retroviruses conferring drug resistance showed that the mature B cells were readily infectable. Moreover, Northern analysis showed that the delta RM-infected mature B cells expressed ras and myc mRNAs to higher levels than the delta RM transformed pre-B cells. Thus, coexpression of ras and myc resulted in the transformation of primary pre-B cells but not of the mature B cells. The potential explanations for the stage-specific transforming activity of the delta RM retrovirus are discussed.