Type I IFN signaling on both B and CD4 T cells is required for protective antibody response to adenovirus.
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.
Zhu
Jiangao
J
Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Huang
Xiaopei
X
Yang
Yiping
Y
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
D000914:Antibodies, Viral; D019496:Cancer Vaccines; D007075:Immunoglobulin M; D007371:Interferon-gamma