Early B-cell activation after West Nile virus infection requires alpha/beta interferon but not antigen receptor signaling.
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/beta) 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/beta receptor.
Purtha
Whitney E
WE
Departments of Medicine, Molecular Microbiology and Pathology & Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8051, St. Louis, MO 63110, USA.
Chachu
Karen A
KA
Virgin
Herbert W
HW
Diamond
Michael S
MS
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D051940:B7-2 Antigen / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D016898:Interferon-alpha / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology*; D037181:Lectins, C-Type; D047589:Leukocyte Reduction Procedures; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011946:Receptors, Antigen / Q000276:immunology*; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D015854:Up-Regulation; D014901:West Nile Fever / Q000276:immunology*; D014902:West Nile virus / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D051940:B7-2 Antigen; D000949:Histocompatibility Antigens Class II; D016898:Interferon-alpha; D016899:Interferon-beta; D037181:Lectins, C-Type; D011946:Receptors, Antigen; D000099192:CD69 Antigens
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