CD40-dependent and -independent activation of human tonsil B cells by CpG oligodeoxynucleotides.
Immunostimulatory CpG oligodeoxynucleotide (CpG-ODN) sequences are known to directly activate B cells. We investigated the expression of the CpG receptor, Toll-like receptor 9 (TLR9), in human tonsil B cells, and determined functional responses following stimulation by a well-characterized stimulatory CpG-containing ODN sequence in the human immune system, ODN 2006. Tonsil B cells were found to express high amounts of TLR9 mRNA and protein, and exposure of B cells to CpG-ODN but not to an inactive control ODN induced a concentration- and time-dependent up-regulation of the activation markers CD23, CD25, CD40, CD54, CD80, CD86 and HLA-DR. However, significant induction of proliferation and the release of IL-6, IL-10, IgG and IgM were only noted when B cells were co-incubated with irradiated CD40L-expressing CHO cells. Endogenous IL-10 was identified as a critical mediator of Ig production, whereas all activating effects were independent of IL-6. Further, CpG-ODN counteracted IgE production induced by IL-4. Collectively, these findings suggest a synergistic role of the TLR9/CD40 system and a critical role for the immunomodulatory cytokine IL-10 in the orchestration of CpG-ODN-induced responses in B lymphocytes.
Gantner
Florian
F
Bayer Yakuhin, Ltd., Research Center Kyoto, Respiratory Diseases Research, Japan. florian.gantner.fg@bayer.co.jp
Hermann
Patrice
P
Nakashima
Kosuke
K
Matsukawa
Satoko
S
Sakai
Katsuya
K
Bacon
Kevin B
KB
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand / Q000502:physiology*; D016466:CHO Cells; D018920:Coculture Techniques; D018899:CpG Islands / Q000276:immunology*; D006224:Cricetinae; D003412:Cricetulus; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D014066:Palatine Tonsil / Q000166:cytology* / Q000276:immunology; D011956:Receptors, Cell Surface / Q000502:physiology*; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D051217:Toll-Like Receptor 9; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D019013:CD40 Antigens; C408982:CPG-oligonucleotide; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D017455:Receptors, IgE; D011993:Recombinant Fusion Proteins; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D016753:Interleukin-10; D023201:CD40 Ligand