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The Journal of Immunology, 2007, 178: 3505-3510.
Copyright © 2007 by The American Association of Immunologists, Inc.

Type I IFN Signaling on Both B and CD4 T Cells Is Required for Protective Antibody Response to Adenovirus1

Jiangao Zhu*, Xiaopei Huang* and Yiping Yang2,*,{dagger}

* Department of Medicine, Division of Medical Oncology, and {dagger} Department of Immunology, Duke University Medical Center, Durham, NC 27710

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by National Institutes of Health Grants CA111807 and CA047741 (to Y.Y.), and an Alliance for Cancer Gene Therapy Grant (to Y.Y.).

2 Address correspondence and reprint requests to Dr. Yiping Yang, Departments of Medicine and Immunology, Duke University Medical Center, Box 3502, Durham, NC 27710. E-mail address: yang0029{at}mc.duke.edu

3 Abbreviations used in this paper: DC, dendritic cell; WT, wild type; PNA, peanut agglutinin.




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