title: Staphylococcus aureus Protein A Disrupts Immunity Mediated by Long-Lived Plasma Cells.
abstract: Infection with Staphylococcus aureus does not induce long-lived protective immunity for reasons that are not completely understood. 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.
authors.affiliation: Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Keener
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15260.
authors.forename: Lance T
authors.initials: LT
authors.lastname: Thurlow
authors.affiliation: Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: SunAh
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Pathology, Massachusetts Medical School, Worcester, MA 01655.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Spidale
authors.affiliation: Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Clarke
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507; and.|Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA 23507.
authors.forename: Kenji M
authors.initials: KM
authors.lastname: Cunnion
authors.affiliation: Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Roland
authors.initials: R
authors.lastname: Tisch
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15260.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Richardson
authors.affiliation: Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; barb_vilen@med.unc.edu.
authors.forename: Barbara J
authors.identifier: 0000-0003-0014-0022
authors.initials: BJ
authors.lastname: Vilen
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory; D018664:Interleukin-12 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000187:drug effects* / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013205:Staphylococcal Protein A / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D013205:Staphylococcal Protein A; D018664:Interleukin-12