title: Efficient induction of cross-presentating human B cell by transduction with human adenovirus type 7 vector.
abstract: Although human autologous B cells represent a promising alternative to dendritic cells (DCs) for easy large-scale preparation, the naive human B cells are always poor at antigen presentation. The safe and effective usage record of human adenovirus type 7 (HAdV7) live vaccines makes it attractive as a promising vaccine vector candidate. To investigate whether HAdV7 vector could be used to induce the human B cells cross-presentation, in the present study, we constructed the E3-defective recombinant HAdV7 vector encoding green fluorescent protein (GFP) and carcinoembryonic antigen (CEA). We demonstrated that naive human B cells can efficiently be transduced, and that the MAPKs/NF-κB pathway can be activated by recombinant HAdV7. We proved that cytokine TNF-α, IL-6 and IL-10, surface molecule MHC class I and the CD86, antigen-processing machinery (APM) compounds ERp57, TAP-1, and TAP-2. were upregulated in HAdV7 transduced human B cells. We also found that CEA-specific IFNγ expression, degranulation, and in vitro and ex vivo cytotoxicities are induced in autologous CD8(+) T cells presensitized by HAd7CEA modified human B cells. Meanwhile, our evidences clearly show that Toll-like receptors 9 (TLR9) antagonist IRS 869 significantly eliminated most of the HAdV7 initiated B cell activation and CD8(+) T cells response, supporting the role and contribution of TLR9 signaling in HAdV7 induced human B cell cross-presentation. Besides a better understanding of the interactions between recombinant HAdV7 and human naive B cells, to our knowledge, the present study provides the first evidence to support the use of HAdV7-modified B cells as a vehicle for vaccines and immunotherapy.
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Laboratory Medicine,Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China.
authors.forename: Meimei
authors.initials: M
authors.lastname: Lai
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Laboratory Medicine,Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Lou
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Laboratory Medicine,Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Laboratory Medicine,Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Laboratory Medicine,Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China. Electronic address: jszhengxq@63.com.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D017503:Adenovirus E3 Proteins / Q000235:genetics; D001402:B-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D045142:Cross-Priming / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D017503:Adenovirus E3 Proteins; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D016328:NF-kappa B; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9
keywords: B cells; Cross-presentation; Human adenovirus type 7; TLR9