Cellular oncogenes and lymphocyte activation.

Abstract

In normal mouse splenic B and T cells at least two cellular proto-oncogenes are expressed, i.e. c-myc and c-fos. The expression of c-myc depends on the activation of the cells, but not on subsequent growth. C-fos gene expression appears to be induced by the manipulation involved in preparation of single cell suspensions from spleens. In that respect, c-fos gene expression does not qualify as being significantly involved in transition from G O to S phase while expression of c-myc seems to be correlated with some early events of cell activation leading to growth competence. The kinetics and extent of c-myc gene expression vary with the mitogen used and the type of lymphocyte investigated as examplified by T cells and subpopulations thereof. The expression of both proto-oncogenes in normal mouse spleen cells is finely regulated by an interplay of transcriptional and post-transcriptional control mechanisms. These mechanisms operate differently for the two genes and independently from one another. They also change in predominance at various times, again independently from one another. While we have no evidence that c-fos has significance for the activation of lymphocytes, c-myc is a good candidate for being involved. Thus studies by Susan Corey and collaborators on transgenic mice which constitutively express c-myc in cells of the lymphocyte lineage, indicate that this lineage is profoundly affected. Among others, the effects concern the balance between proliferation and maturation and a constitutive high level of Ia expression, normally only observed in activated cells. Constitutive high expression of c-myc in B cells of these transgenic mice also makes them prone to leukemia possibly due to a series of subsequent events. These last findings also provide an explanation for the need for a very finely tuned regulation of c-myc gene expression as it is here described.