Cytosine–phosphate–guanosine‐DNA induces CD274 expression in human B cells and suppresses T helper type 2 cytokine production in pollen antigen‐stimulated CD4‐positive cells

Summary Co‐stimulatory molecules are important for regulating T cell activation and immune response. CD274 [programmed death ligand 1 (PD‐L1), B7‐H1] has emerged as an important immune modulator that can block T cell receptor signalling. We have investigated whether PD‐L1 and other co‐stimulatory ligands could be expressed in human B cells stimulated by cytosine–phosphate–guanosine (CpG)‐DNA. CpG‐DNA strongly induced the co‐inhibitory molecule ligand, PD‐L1, of human B cells. Results show that nuclear factor‐kappa B (NF‐κB) signalling is involved directly in CpG‐DNA‐induced PD‐L1 expression in human B cells. We sought to determine the effect of CpG‐DNA‐treated B cells on T helper type 2 (Th2) cytokine production in Cry j 1 (Japanese pollen antigen)‐stimulated human CD4‐positive cells from patients with seasonal allergic rhinitis caused by Japanese cedar pollen. CpG‐DNA‐treated B cells reduced Cry j 1‐induced interleukin (IL)‐5 and IL‐13 production in CD4‐positive cells. When the binding of PD‐1 to PD‐L1 was inhibited by PD‐1‐immunoglobulin (Ig), this chimera molecule reversed the previously described reductions in IL‐5 and IL‐13 production. In contrast, the CpG B‐treated B cells increased both interferon (IFN)‐γ and IL‐12 production in the presence of Cry j 1‐stimulated CD4‐positive cells. CpG‐DNA simultaneously reduced the expression of B7RP‐1 [also known as inducible co‐stimulator ligand (ICOSL), B7‐H2] and the ligand of CD30 (CD30L). These results indicate that CpG‐DNA induces co‐inhibitory molecule ligand PD‐L1 expression in human B cells and PD‐L1 can suppress Th2 cytokine production in Cry j 1‐stimulated CD4‐positive cells, while CpG‐DNA increased Th1 cytokine production and reduced the expression of co‐stimulatory molecule ligands that can promote Th2 inflammatory responses.