Epstein‐barr virus (EBV) nuclear‐antigen‐2‐induced up‐regulation of cd21 and cd23 molecules is dependent on a permissive cellular context

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Abstract
The Epltein‐Barr virus (EBV) induces unlimited growth of B lymphocytes in vitro, a phenomenon known as immortalization. The elucidation of the mechanisms by which EBV de‐regulates 8‐cell protiiferation in vitro will permit an undemtanding of how the vim contributes in vivo to the genesis of Burkitt's lym‐ phoma (BL) and of lymphopmliierations in immunosuppressed patients. At present, no singie EBV immortalizing gene has been identified, and the hypothesis has been made that many viral genes cooperate in establishing an autocrine loop of secretion leading to irnmortdization. Constitutive expression of B‐cell surface molecules such as CD2l and CD23, specifically impli‐ cated in the control of B‐cell proliferation, is indeed induced at the surface of immortalized B lymphocytes. The expression of the v i d nuclear antigen 2 (EBNA2) has been shown to be in part responsible for CD2l and CD23 upregulation, and EBNA2 is suspected to be a transactivahr of cellular genes, although this point remains to be demonstrated. The role of EBNA2 gene, independently of other vim1 genes, has beeriinvestigated by transfeetion into B‐lymphoma lines, but conflicting results have been reported. To further investigate its role in the regulation ofCD2l and CD23 molecules, we have compared the effects of EBNA2 expression in 2 sets of B‐lymphoma lines infected with P3HRI EBV strain, and/or tmnsfected with EBNA2 gene. We report here that: (i) EBNAZ expression is not a sufficient conditiw to induce CD21 and CD23 upregulation, EBNA2′s effects are highly dependent on the cellular context, and momover can be modffied by infection with P3HRl virus; (ii) EBNA2 inducer acthation of CD23 expression in a very pvticutar way, namely, an increased quantity of CD23 steady‐ state RNA coding for the form A of the protein, which is not detectable at the cell surface but directly secreted. ® 1993 Wiley‐Liss, Inc.