Blocked B cell differentiation and emigration support the early growth of Myc-induced lymphomas

Avian leukosis virus induces lymphoma in chickens after proviral integratio n within the c-Myc gene, and subsequent expansion of Myc-overexpressing lym phocytes within transformed bursal follicles, The clonal expansion of these follicles allowed us to examine how Myc influences cell differentiation, g rowth, and apoptosis in lymphoid progenitors soon after the onset of Myc ov erexpression, Immunohistochemical analysis of developmental markers establi shed that Myc overexpression consistently blocks lymphocyte differentiation at a late embryonic stage. Myc-transformed follicles also grow much more r apidly than normal follicles, This rapid growth is not mediated by suppress ion of apoptosis, as normal and Myc-transformed follicles showed similar ra tes of cell death by TUNEL immunohistochemical analyis of cells undergoing DNA degradation. Measurements of DNA synthesis and mitotic index showed mod est effects of Myc to increase lymphocyte proliferation, as normal lymphocy tes already divide rapidly. The major mechanism mediating rapid growth of t ransformed follicles instead involved failure of myc-overexpressing lymphoc ytes to emigrate from transformed follicles, while normal lymphocytes activ ely emigrate after hatching, as measured by BrdU pulse-chase labeling and i mmunohistochemical measurements. This failure to undergo the normal program of differentiation and subsequent bursal retention of lymphocytes accounts for most of the growth of transformed follicles, while Myc-induced prolife ration makes a smaller contribution.