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Editor, Senior Moderator
Citation: Boyden AW, Legge KL, Waldschmidt TJ (2012) Pulmonary Infection with Influenza A Virus Induces Site-Specific Germinal Center and T Follicular Helper Cell Responses. PLoS ONE 7(7): e40733. doi:10.1371/journal.pone.0040733
Alexander W. Boyden1,2, Kevin L. Legge1,2,3, Thomas J. Waldschmidt1,2*
1 Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America, 2 Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America, 3 Department of Microbiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America
Abstract Top
Protection from influenza A virus (IAV) challenge requires switched, high affinity Abs derived from long-lived memory B cells and plasma cells. These B cell subsets are generated in germinal centers (GCs), hallmark structures of T helper cell-driven B cell immunity. A full understanding of the GC reaction after respiratory IAV infection is lacking, as is the characterization of T follicular helper (TFH) cells that support GCs. Here, GC B cell and TFH cell responses were studied in mice following pulmonary challenge with IAV. Marked GC reactions were induced in draining lymph nodes (dLNs), lung, spleen and nasal-associated lymphoid tissue (NALT), although the magnitude and kinetics of the response was site-specific. Examination of switching within GCs demonstrated IgG2+ cells to compose the largest fraction in dLNs, lung and spleen. IgA+ GC B cells were infrequent in these sites, but composed a significant subset of the switched GC population in NALT. Further experiments demonstrated splenectomized mice to withstand a lethal recall challenge, suggesting the spleen to be unnecessary for long-term protection in spite of strong GC responses in this organ. Final studies showed that TFH cell numbers were highest in dLNs and spleen, and peaked in all sites prior to the height of the GC reaction. TFH cells purified from dLNs generated IL-21 and IFNγ upon activation, although CD4+CXCR5− T effector cells produced higher levels of all cytokines. Collectively, these findings reveal respiratory IAV infection to induce strong T helper cell-driven B cell responses in various organs, with each site displaying unique attributes.
http://www.plosone.org/article/info...3;jsessionid=7921CF436175B2458845242B1C017B69
Alexander W. Boyden1,2, Kevin L. Legge1,2,3, Thomas J. Waldschmidt1,2*
1 Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America, 2 Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America, 3 Department of Microbiology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America
Abstract Top
Protection from influenza A virus (IAV) challenge requires switched, high affinity Abs derived from long-lived memory B cells and plasma cells. These B cell subsets are generated in germinal centers (GCs), hallmark structures of T helper cell-driven B cell immunity. A full understanding of the GC reaction after respiratory IAV infection is lacking, as is the characterization of T follicular helper (TFH) cells that support GCs. Here, GC B cell and TFH cell responses were studied in mice following pulmonary challenge with IAV. Marked GC reactions were induced in draining lymph nodes (dLNs), lung, spleen and nasal-associated lymphoid tissue (NALT), although the magnitude and kinetics of the response was site-specific. Examination of switching within GCs demonstrated IgG2+ cells to compose the largest fraction in dLNs, lung and spleen. IgA+ GC B cells were infrequent in these sites, but composed a significant subset of the switched GC population in NALT. Further experiments demonstrated splenectomized mice to withstand a lethal recall challenge, suggesting the spleen to be unnecessary for long-term protection in spite of strong GC responses in this organ. Final studies showed that TFH cell numbers were highest in dLNs and spleen, and peaked in all sites prior to the height of the GC reaction. TFH cells purified from dLNs generated IL-21 and IFNγ upon activation, although CD4+CXCR5− T effector cells produced higher levels of all cytokines. Collectively, these findings reveal respiratory IAV infection to induce strong T helper cell-driven B cell responses in various organs, with each site displaying unique attributes.
http://www.plosone.org/article/info...3;jsessionid=7921CF436175B2458845242B1C017B69