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essential step in the development of effective antiviral humoral responses is cytokine-triggered class switch recombination resulting in the production of antibodies of a specific isotype. Most viral and parasitic infections in mice induce predominantly IgG2a-specific antibody responses that are stimulated by interferon gamma (IFN-\u03b3). However, in some mice deficient in IFN-\u03b3, class switching to IgG2a antibodies is relatively unaffected, indicating that another signal(s) can be generated upon viral or parasitic infections that trigger this response. Here, we found that a single recessive locus, provisionally called IFN-\u03b3-independent IgG2a (Igii), confers the ability to produce IFN-\u03b3-independent production of IgG2a antibodies upon retroviral infection. The Igii locus was mapped to chromosome 9 and was found to function in the radiation-resistant compartment. Thus, our data implicate nonhematopoietic cells in activation of antiviral antibody responses in the absence of IFN-\u03b3.IMPORTANCE Understanding the signals that stimulate antibody production and class switch recombination to specific antibody isotypes is crucial for the development of novel vaccines and adjuvants. While an interferon gamma-mediated switch to the IgG2a isotype upon viral infection in mice has been well established, this investigation reveals a noncanonical, interferon gamma-independent pathway for antiretroviral antibody production and IgG2a class switch recombination that is controlled by a single recessive locus. Furthermore, this study indicates that the radiation-resistant compartment can direct antiviral antibody responses, suggesting that detection of infection by nonhematopoietic cells is involved is stimulating adaptive immunity.","bibjson":{"author":[{"initials":"Y","lastname":"Shi","name":"Shi Y"},{"initials":"A","lastname":"Kawana-Tachikawa","name":"Kawana-Tachikawa A"},{"initials":"F","lastname":"Gao","name":"Gao F"},{"initials":"J","lastname":"Qi","name":"Qi J"},{"initials":"C","lastname":"Liu","name":"Liu C"},{"initials":"J","lastname":"Gao","name":"Gao J"},{"initials":"H","lastname":"Cheng","name":"Cheng H"},{"initials":"T","lastname":"Ueno","name":"Ueno T"},{"initials":"A","lastname":"Iwamoto","name":"Iwamoto A"},{"initials":"GF","lastname":"Gao","name":"Gao GF"}],"identifier":[{"id":"10.1128/JVI.00725-17","type":"doi"},{"id":"28615212","type":"pubmed"}],"issue":[null],"journal":{"iso_abbreviation":"J. 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