Presentation of soluble antigens to CD8+ T cells by CpG oligodeoxynucleotide-primed human naive B cells.
Naive B lymphocytes are generally thought to be poor APCs, and there is limited knowledge of their role in activation of CD8(+) T cells. In this article, we demonstrate that class I MHC Ag presentation by human naive B cells is enhanced by TLR9 agonists. Purified naive B cells were cultured with or without a TLR9 agonist (CpG oligodeoxynucleotide [ODN] 2006) for 2 d and then assessed for phenotype, endocytic activity, and their ability to induce CD8(+) T cell responses to soluble Ags. CpG ODN enhanced expression of class I MHC and the costimulatory molecule CD86 and increased endocytic activity as determined by uptake of dextran beads. Pretreatment of naive B cells with CpG ODN also enabled presentation of tetanus toxoid to CD8(+) T cells, resulting in CD8(+) T cell cytokine production and granzyme B secretion and proliferation. Likewise, CpG-activated naive B cells showed enhanced ability to cross-present CMV Ag to autologous CD8(+) T cells, resulting in proliferation of CMV-specific CD8(+) T cells. Although resting naive B cells are poor APCs, they can be activated by TLR9 agonists to serve as potent APCs for class I MHC-restricted T cell responses. This novel activity of naive B cells could be exploited for vaccine design.
Division of Infectious Diseases and HIV Medicine, Case Western Reserve University, University Hospitals/Case Medical Center, Cleveland, OH 44106, USA. wei.jiang@case.edu
Wei
W
Jiang
Michael M
MM
Lederman
Clifford V
CV
Harding
Scott F
SF
Sieg
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D045142:Cross-Priming / Q000276:immunology*; D004705:Endocytosis / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D016192:Resting Phase, Cell Cycle / Q000276:immunology*; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000378:metabolism
D000276:Adjuvants, Immunologic; D051940:B7-2 Antigen; C497964:CD86 protein, human; C513533:CpG ODN 2006; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9
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