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Sequential or overlapping coinfections with both pathogens are common, yet the impact of coinfection on the generation and maintenance of Ab responses is largely unknown. We report here that the B cell response to IAV is altered in mice coinfected with IAV and<jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>and that this response differs, depending on the order of pathogen exposure. In mice exposed to<jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>prior to IAV, the initial virus-specific germinal center (GC) B cell response is significantly enhanced in the lung-draining mediastinal lymph node and spleen, and there is an increase in CD4<jats:sup>+<\/jats:sup>T follicular helper (TFH) cell numbers. In contrast, secondary<jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>infection exaggerates early antiviral antibody-secreting cell formation, and at later times, levels of GCs, TFH cells, and antiviral serum IgG are elevated. Mice exposed to<jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>prior to IAV do not maintain the initially robust GC response in secondary lymphoid organs and exhibit reduced antiviral serum IgG with diminished virus neutralization activity a month after infection. Our data suggest that the history of pathogen exposures can critically affect the generation of protective antiviral Abs and may partially explain the differential susceptibility to and disease outcomes from IAV infection in humans.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Respiratory tract coinfections, specifically those involving influenza A viruses and<jats:named-content content-type=\"genus-species\">Streptococcus pneumoniae<\/jats:named-content>, remain a top global health burden. We sought to determine how<jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>coinfection modulates the B cell immune response to influenza virus since antibodies are key mediators of protection.<\/jats:p>","DOI":"10.1128\/jvi.01833-14","type":"journal-article","created":{"date-parts":[[2014,8,7]],"date-time":"2014-08-07T05:11:35Z","timestamp":1407388295000},"page":"11995-12005","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Coinfection with Streptococcus pneumoniae Modulates the B Cell Response to Influenza Virus"],"prefix":"10.1128","volume":"88","author":[{"given":"Amaya I.","family":"Wolf","sequence":"first","affiliation":[{"name":"The Wistar Institute, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura C.","family":"Strauman","sequence":"additional","affiliation":[{"name":"The Wistar Institute, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystyna","family":"Mozdzanowska","sequence":"additional","affiliation":[{"name":"The Wistar Institute, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R. 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