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Journal of Virology, November 2008, p. 10964-10974, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01646-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Early B-Cell Activation after West Nile Virus Infection Requires Alpha/Beta Interferon but Not Antigen Receptor Signaling{triangledown}

Whitney E. Purtha,1 Karen A. Chachu,1 Herbert W. Virgin IV,1 and Michael S. Diamond1,2,3*

Pathology & Immunology,1 Medicine,2 Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 631103

Received 1 August 2008/ Accepted 4 September 2008

The B-cell response against West Nile virus (WNV), an encephalitic Flavivirus of global concern, is critical to controlling central nervous system dissemination and neurological sequelae, including death. Here, using a well-characterized mouse model of WNV infection, we examine the factors that govern early B-cell activation. Subcutaneous inoculation with a low dose of replicating WNV results in extensive B-cell activation in the draining lymph node (LN) within days of infection as judged by upregulation of the surface markers CD69, class II major histocompatibility complex, and CD86 on CD19+ cells. B-cell activation in the LN but not the spleen was dependent on signals through the type I alpha/beta interferon (IFN-{alpha}/β) receptor. Despite significant activation in the draining LN at day 3 after infection, WNV-specific B cells were not detected by immunoglobulin M enzyme-linked immunospot analysis until day 7. Liposome depletion experiments demonstrate that B-cell activation after WNV infection was not affected by the loss of F4/80+ or CD169+ subcapsular macrophages. Nonetheless, LN myeloid cells were essential for control of viral replication and survival from infection. Overall, our data suggest that the massive, early polyclonal B-cell activation occurring in the draining LN after WNV infection is immunoglobulin receptor and macrophage independent but requires sustained signals through the type I IFN-{alpha}/β receptor.

* Corresponding author. Mailing address: Departments of Medicine, Molecular Microbiology and Pathology & Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8051, St. Louis, MO 63110. Phone: (314) 362-2842. Fax: (314) 362-9230. E-mail: diamond{at}borcim.wustl.edu

{triangledown} Published ahead of print on 10 September 2008.

Journal of Virology, November 2008, p. 10964-10974, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01646-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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