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. 2012 Jul 1;189(1):181-90. doi: 10.4049/jimmunol.1102277. Epub 2012 Jun 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / pathology
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / biosynthesis
  • B7-H1 Antigen / physiology*
  • Biological Transport, Active / immunology
  • Cell Death / immunology
  • Cell Line
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Cell Survival / immunology
  • Down-Regulation / immunology
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Killer Cells, Natural / immunology*
  • Lysosomes / immunology
  • Lysosomes / metabolism*
  • Proto-Oncogene Proteins c-myc / physiology*
  • RNA, Messenger / genetics
  • RNA, Viral / physiology*
  • T-Lymphocyte Subsets / immunology*
  • Virus Latency / immunology*


  • B7-H1 Antigen
  • CD274 protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • RNA, Viral