title: PD-1 is a novel regulator of human B-cell activation.
abstract: The outcome of the adaptive immune response is determined by the integration of both positive and negative signals, respectively, induced upon the triggering of co-signaling receptors. One of them, programmed cell death 1 (PDCD1/PD-1) has largely been shown to be involved in the negative regulation of T-cell activation. However, PD-1 is also expressed on human B cells, and its role(s) in the process of human B-cell activation remains uncertain thus far. In this study, we describe the expression of PD-1 on the major human B-cells subsets isolated from peripheral blood and lymph nodes. We showed that PD-1 was expressed on naive B cells, was differentially expressed on peripheral IgM memory as compared with memory B cells and was lost on germinal center B cells. Expression of PD-1 ligands (PD-Ls) was induced by TLR9 activation. Finally, we showed that PD-1 was recruited to the B-cell receptor upon triggering. We determined that during TLR9 activation, blockade of PD-1/PD-Ls pathways indeed increased B-cell activation, proliferation and the production of inflammatory cytokines. Altogether, our results show, that, as reported in T cells, PD-1/PD-Ls complexes acted as inhibitors of the B-cell activation cascade and highlight the importance of devising future therapies able to modulate lymphocyte activation through the targeting of the PD-1/PD-Ls pathways.
authors.affiliation: Inserm U1068,  Centre de Recherche en Cancerologie de Marseille, F-13009 Marseille,  France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Thibult
authors.forename: Emilie
authors.initials: E
authors.lastname: Mamessier
authors.forename: Julie
authors.initials: J
authors.lastname: Gertner-Dardenne
authors.forename: Sonia
authors.initials: S
authors.lastname: Pastor
authors.forename: Sylvaine
authors.initials: S
authors.lastname: Just-Landi
authors.forename: Luc
authors.initials: L
authors.lastname: Xerri
authors.forename: Bruno
authors.initials: B
authors.lastname: Chetaille
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis / Q000276:immunology*
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor