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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.

Type I IFN Signaling on Both B and CD4 T Cells Is Required for Protective Antibody Response to Adenovirus