Epstein-Barr virus latent membrane protein (LMP1) is not sufficient to maintain proliferation of B cells but both it and activated CD40 can prolong their survival.
Epstein-Barr virus (EBV) infects human primary B lymphocytes and induces and maintains proliferation of these cells efficiently in vitro. Mutants of Epstein-Barr virus which express EBV nuclear antigen 2 (EBNA2) in a conditional fashion allow dissection of individual contributions of viral genes to B cell immortalization. EBNA2 is a transcriptional activator of cellular and viral genes, including the viral latent membrane protein 1 (LMP1), which is essential for B cell immortalization and has oncogenic effects in non-lymphoid cells. To analyze the role of this gene in B cell immortalization, LMP1 was constitutively expressed in B cells infected with EBV carrying a conditional EBNA2 allele. In the absence of functional EBNA2, LMP1 was incapable of sustaining B cell proliferation in two independent assays but induced a phenotype consistent with prolonged cell viability. Activation of CD40 displayed a comparable phenotype. These data indicate that both CD40 activation and LMP1 expression may use a common pathway for B cell activation. Proliferation of human B cells, however, requires one or more additional signals triggered by EBNA2.
Zimber-Strobl
U
U
GSF-National Research Center for Environment and Health, Institut für Klinische Molekularbiologie und Tumorgenetik, Munchen, Germany.
Kempkes
B
B
Marschall
G
G
Zeidler
R
R
Van Kooten
C
C
Banchereau
J
J
Bornkamm
G W
GW
Hammerschmidt
W
W
D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000502:physiology; D004261:DNA Replication; D004967:Estrogens / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D015398:Signal Transduction; D014763:Viral Matrix Proteins / Q000378:metabolism / Q000502:physiology*
D019013:CD40 Antigens; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D004967:Estrogens; D014763:Viral Matrix Proteins