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. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Immunology Année : 2012

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.

Résumé

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.

Domaines

Immunologie

Dates et versions

hal-00716804 , version 1 (11-07-2012)

Identifiants

Citer

Stéphanie Durand-Panteix, Mona Farhat, Ibtissam Youlyouz-Marfak, Pauline Rouaud, Catherine Ouk-Martin, et al.. 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.. Journal of Immunology, 2012, 189 (1), pp.181-90. ⟨10.4049/jimmunol.1102277⟩. ⟨hal-00716804⟩
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