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CpG-ODN-induced sustained expression of BTLA mediating selective inhibition of human B cells

Thibult, Marie-Laure ; Rivals, Jean-Paul ; Mamessier, Emilie ; Gertner-Dardenne, Julie ; Pastor, Sonia ; Speiser, Daniel ; Derré, Laurent ; Olive, Daniel

In: Journal of Molecular Medicine, 2013, vol. 91, no. 2, p. 195-205

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    Titre
    • CpG-ODN-induced sustained expression of BTLA mediating selective inhibition of human B cells
    Auteur
    • Thibult, Marie-Laure. INSERM U1068, Centre de Recherche en Cancérologie de Marseille, 13009, Marseille, France
    • Rivals, Jean-Paul. Department of Otolaryngology and Head and Neck Surgery, University Hospital Center and University of Lausanne (CHUV), Lausanne, Switzerland
    • Mamessier, Emilie. INSERM U1068, Centre de Recherche en Cancérologie de Marseille, 13009, Marseille, France
    • Gertner-Dardenne, Julie. INSERM U1068, Centre de Recherche en Cancérologie de Marseille, 13009, Marseille, France
    • Pastor, Sonia. INSERM U1068, Centre de Recherche en Cancérologie de Marseille, 13009, Marseille, France
    • Speiser, Daniel. Clinical Tumor Biology and Immunotherapy Unit, Ludwig Center of the University of Lausanne, Lausanne, Switzerland
    • Derré, Laurent. Urology Research Unit c/o IMUL, Department of Urology, University Hospital of Lausanne, (CHUV), rue du Bugnon 48, CH-1011, Lausanne, Switzerland
    • Olive, Daniel. INSERM U1068, Centre de Recherche en Cancérologie de Marseille, 13009, Marseille, France
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Journal of Molecular Medicine, 2013, vol. 91, no. 2, p. 195-205. Springer-Verlag
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:315117
    Summary
    BTLA (B- and T-lymphocyte attenuator) is a prominent co-receptor that is structurally and functionally related to CTLA-4 and PD-1. In T cells, BTLA inhibits TCR-mediated activation. In B cells, roles and functions of BTLA are still poorly understood and have never been studied in the context of B cells activated by CpG via TLR9. In this study, we evaluated the expression of BTLA depending on activation and differentiation of human B cell subsets in peripheral blood and lymph nodes. Stimulation with CpG upregulated BTLA, but not its ligand: herpes virus entry mediator (HVEM), on B cells in vitro and sustained its expression in vivo in melanoma patients after vaccination. Upon ligation with HVEM, BTLA inhibited CpG-mediated B cell functions (proliferation, cytokine production, and upregulation of co-stimulatory molecules), which was reversed by blocking BTLA/HVEM interactions. Interestingly, chemokine secretion (IL-8 and MIP1β) was not affected by BTLA/HVEM ligation, suggesting that BTLA-mediated inhibition is selective for some but not all B cell functions. We conclude that BTLA is an important immune checkpoint for B cells, as similarly known for T cells