B7-H1, which represses EBV-immortalized B cell killing by autologous T and NK cells, is oppositely regulated by c-Myc and EBV latency III program at both mRNA and secretory lysosome levels.
J Immunol
; 189(1): 181-90, 2012 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-22661084
EBV-immortalized B cells induce a complex immune response such that the virus persists as a clinically silent infection for the lifetime of the infected host. B7-H1, also called PD-L1, is a cosignaling molecule of the B7 family that can inhibit activated T cell effectors by interaction with its receptor PD-1. In this work, we have studied the dependence of B7-H1 on NF-κB and c-Myc, the two main transcription factors in EBV latency III proliferating B cells, on various lymphoblastoid and Burkitt lymphoma cell lines, some of them being inducible or not for the EBV latency III program and/or for c-Myc. We found that B7-H1 repressed killing of EBV-immortalized B cells by their autologous T and NK cells. At the mRNA level, NF-κB was a weak inducer whereas c-Myc was a strong repressor of B7-H1 expression, an effect mediated by STAT1 inhibition. At the protein level, B7-H1 molecules were stored in both degradative and unconventional secretory lysosomes. Surface membrane B7-H1 molecules were constitutively internalized and proteolyzed in lysosomes. The EBV latency III program increased the amounts of B7-H1-containing secretory lysosomes and their export to the surface membrane. By repressing actin polymerization, c-Myc blocked secretory lysosome migration and B7-H1 surface membrane export. In addition to B7-H1, various immunoregulatory molecules participating in the immunological synapse are stored in secretory lysosomes. By playing on actin polymerization, c-Myc could thus globally regulate the immunogenicity of transformed B cells, acting on export of secretory lysosomes to plasma membrane.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ARN Viral
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Células Asesinas Naturales
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Subgrupos de Linfocitos B
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Subgrupos de Linfocitos T
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Proteínas Proto-Oncogénicas c-myc
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Latencia del Virus
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Herpesvirus Humano 4
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Antígeno B7-H1
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Lisosomas
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Estados Unidos