EPSTEIN-BARR-VIRUS LATENT MEMBRANE-PROTEIN (LMP1) IS NOT SUFFICIENT TO MAINTAIN PROLIFERATION OF B-CELLS BUT BOTH IT AND ACTIVATED CD40 CANPROLONG THEIR SURVIVAL

Epstein-Barr virus (EBV) infects human primary B lymphocytes and induc es and maintains proliferation of these cells efficiently in vitro. Mu tants of Epstein-Barr virus which express EBV nuclear antigen 2 (EBNA2 ) in a conditional fashion allow dissection of individual contribution s of viral genes to B cell immortalization. EBNA2 is a transcriptional activator of cellular and viral genes, including the viral latent mem brane protein 1 (LMP1), which is essential for B cell immortalization and has oncogenic effects in nonlymphoid cells. To analyze the role of this gene in B cell immortalization, LMP1 was constitutively expresse d in B cells infected with EBV carrying a conditional EBNA2 allele. In the absence of functional EBNA2, LMP1 was incapable of sustaining B c ell proliferation in two independent assays but induced a phenotype co nsistent with prolonged cell viability. Activation of CD40 displayed a comparable phenotype. These data indicate that both CD40 activation a nd LMP1 expression may use a common pathway for B cell activation, Pro liferation of human B cells, however, requires one or more additional signals triggered by EBNA2.