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Inhibition of B‐cell activation and antibody production by triggering inhibitory signals via the PD ‐1/ PD ‐ligand pathway
Author(s) -
Buermann Anna,
Römermann Dorothee,
Baars Wiebke,
Hundrieser Joachim,
Klempnauer Jürgen,
Schwinzer Reinhard
Publication year - 2016
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12261
Subject(s) - antibody , receptor , cpg oligodeoxynucleotide , microbiology and biotechnology , downregulation and upregulation , peripheral blood mononuclear cell , epitope , biology , stimulation , t cell , cell culture , chemistry , immune system , in vitro , immunology , biochemistry , endocrinology , genetics , gene expression , dna methylation , gene
Background The development of donor‐reactive antibodies is regarded to be an important barrier limiting long‐term outcome of allo‐ and xenografts. We asked whether enhanced signaling via the co‐inhibitory receptor programmed cell death‐1 ( PD ‐1; CD 279) can downregulate human B‐cell activation. Methods Proliferation of human purified CD 19 + B cells was induced by in vitro stimulation with CpG oligodeoxynucleotides (CpG‐B). To induce antibody production, peripheral blood mononuclear cells were co‐cultured with the porcine B‐cell line L23. Triggering of inhibitory signals via the PD ‐1 receptor was obtained either using a recombinant agonistic soluble ligand ( PD ‐L1.Ig) or L23 transfectants overexpressing membrane‐bound human PD ‐L1 ( CD 274; L23‐ PD ‐L1 cells). Results Stimulation of purified CD 19 + B cells with CpG‐B resulted in upregulation of PD ‐1 and strong proliferation. Addition of PD ‐L1.Ig significantly reduced B‐cell proliferation in a dose‐dependent manner. A great proportion (~1%) of human circulating B cells recognizes the epitope galactose‐α1,3‐galactose‐β1,4‐N‐acetylglucosamine‐R (α‐gal). Thus, when B cells—in the presence of T cell help—were cocultured with α‐gal‐expressing L23 cells, anti‐gal and anti‐L23 antibodies could readily be detected in the culture supernatant. The level of induced antibodies was significantly reduced when stimulation was performed by L23‐ PD ‐L1 cells. Conclusions Enhancing inhibitory signals may be part of future protocols to better control humoral immunity to allo‐ and xenografts.