The first goal is to determine which of the oncogenes we have found to be expressed in B cell neoplasms are capable, either individually or in pairs, of neutralizing normal cell cycle restriction points controlling B lymphocyte growth. The second goal is to address the need for cloned normal B cells in sufficient quantity to study in molecular detail the events of B cells activation (growth and differentiation) and inactivation (tolerance and suppression). The lack of such populations has to date hindered progress in the study of B cell growth and differentiation factors, the receptors for these factors and their mechanisms of action. In comparison, the availability of non-transformed antigen-specific helper T cell clones and cytotoxic T cell clones have made the detailed study of these parameters in the T cell lineage possible. The current status of the biochemistry of B cell activation and inactivation demonstrates the need for such a system. Our focus with the cloned B cell populations we generate will be to pursue our studies on the regulation of B cell growth. Both of these goals will be addressed using hybrid genes constructed with the micro-enhancer to ensure expression of the promoter-linked genes in B cells and a regulatable promoter controlling the expression of an oncogene. Removal of the agent used to activate the promoter should shut down synthesis of the oncogene product providing a conditionally """"""""normal"""""""" cell population which will allow the study of parameters involved in B cell growth. The advantages of the inducible oncogene are several. A large number of cells may be grown while the promoter is induced, thus generating as many cells as needed for biochemical and molecular genetic experiments. In addition, a direct comparison of normal growth with transformed growth parameters may be performed using the same clonal population of cells.
| DeCino, P; Lernhardt, W; Herbst, H et al. (1988) Expression of oncogenes in normal and transformed murine B lymphocytes. Oncogene Res 3:33-7 |
