title: Type I IFN signaling on both B and CD4 T cells is required for protective antibody response to adenovirus.
abstract: Recombinant adenoviruses have been used as vehicles for gene therapy as well as vaccination against infectious diseases and cancer. Efficient activation of host B cell response to adenoviral vectors that leads to the generation of protective, neutralizing Ab, represents a major barrier for gene therapy, but an attractive feature for vaccine development. What regulate(s) potent B cell response to adenoviral vectors remains incompletely defined. In this study, we showed that type I IFNs induced upon adenoviral infection are critical for multiple stages of adaptive B cell response to adenovirus including early B cell activation, germinal center formation, Ig isotype switching as well as plasma cell differentiation. We further demonstrated that although type I IFN signaling on dendritic cells was important for the production of virus-specific IgM, the generation of protective neutralizing Ab critically depended on type I IFN signaling on both CD4 T and B cells. The results may suggest potential strategies for improving adenovirus-mediated gene therapy in vivo and/or the design of effective vaccines for cancer and infectious diseases.
authors.affiliation: Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jiangao
authors.initials: J
authors.lastname: Zhu
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Huang
authors.forename: Yiping
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000276:immunology; D018858:Germinal Center / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D010950:Plasma Cells / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019496:Cancer Vaccines; D007075:Immunoglobulin M; D007371:Interferon-gamma