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Human and murine vaccine studies support a role for Abs in protecting against recurring infections, but S. aureus modulates the B cell response through expression of staphylococcus protein A (SpA), a surface protein that drives polyclonal B cell expansion and induces cell death in the absence of costimulation. In this murine study, we show that SpA altered the fate of plasmablasts and plasma cells (PCs) by enhancing the short-lived extrafollicular response and reducing the pool of bone marrow (BM)-resident long-lived PCs. The absence of long-lived PCs was associated with a rapid decline in Ag-specific class-switched Ab. In contrast, when previously inoculated mice were challenged with an isogenic SpA-deficient S. aureus mutant, cells proliferated in the BM survival niches and sustained long-term Ab titers. The effects of SpA on PC fate were limited to the secondary response, because Ab levels and the formation of B cell memory occurred normally during the primary response in mice inoculated with wild-type or SpA-deficient S. aureus mutant. Thus, failure to establish long-term protective Ab titers against S. aureus was not a consequence of diminished formation of B cell memory; instead, SpA reduced the proliferative capacity of PCs that entered the BM, diminishing the number of cells in the long-lived pool.<\/jats:p>","DOI":"10.4049\/jimmunol.1600093","type":"journal-article","created":{"date-parts":[[2016,12,28]],"date-time":"2016-12-28T21:00:16Z","timestamp":1482958816000},"page":"1263-1273","source":"Crossref","is-referenced-by-count":43,"title":["<i>Staphylococcus aureus<\/i>\n                    Protein A Disrupts Immunity Mediated by Long-Lived Plasma Cells"],"prefix":"10.1093","volume":"198","author":[{"given":"Amanda B","family":"Keener","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance T","family":"Thurlow","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh , Pittsburgh, PA 15260"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SunAh","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A","family":"Spidale","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji M","family":"Cunnion","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School , Norfolk, VA 23507"},{"name":"Department of Physiological Sciences, Eastern Virginia Medical School , Norfolk, VA 23507"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Tisch","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh , Pittsburgh, PA 15260"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0014-0022","authenticated-orcid":false,"given":"Barbara J","family":"Vilen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,2,1]]},"reference":[{"key":"2025030615015264000_r1","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1086\/591698","article-title":"The impact of antimicrobial-resistant, health care-associated infections on mortality in the United States","volume":"47","author":"Klevens","year":"2008","journal-title":"Clin. 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