title: Direct visualization of endogenous Salmonella-specific B cells reveals a marked delay in clonal expansion and germinal center development.
abstract: CD4(+) T cells and B cells are both essential for acquired immunity to Salmonella infection. It is well established that Salmonella inhibit host CD4(+) T-cell responses, but a corresponding inhibitory effect on B cells is less well defined. Here, we utilize an Ag tetramer and pull-down enrichment strategy to directly visualize OVA-specific B cells in mice, as they respond to infection with Salmonella-OVA. Surprisingly, OVA-specific B-cell expansion and germinal center formation was not detected until bacteria were cleared from the host. Furthermore, Salmonella infection also actively inhibited both B- and T-cell responses to the same coinjected Ag but this did not require the presence of iNOS. The Salmonella Pathogenicity Island 2 (SPI2) locus has been shown to be responsible for inhibition of Salmonella-specific CD4(+) T-cell responses, and an examination of SPI2-deficient bacteria demonstrated a recovery in B-cell expansion in infected mice. Together, these data suggest that Salmonella can simultaneously inhibit host B- and T-cell responses using SPI2-dependent mechanisms.
authors.affiliation: Center for Comparative Medicine, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, CA, USA; Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota Medical School-Twin Cities, Minneapolis, MN, USA.
authors.forename: Minelva R
authors.initials: MR
authors.lastname: Nanton
authors.forename: Seung-Joo
authors.initials: SJ
authors.lastname: Lee
authors.forename: Shaikh M
authors.initials: SM
authors.lastname: Atif
authors.forename: Sean-Paul
authors.initials: SP
authors.lastname: Nuccio
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Taylor
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
authors.forename: Sing Sing
authors.initials: SS
authors.lastname: Way
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McSorley
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D049109:Cell Proliferation; D002999:Clone Cells; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression; D018858:Germinal Center / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D054884:Host-Pathogen Interactions; D007114:Immunization; D016130:Immunophenotyping; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology*; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C440638:SPI-2 protein, Salmonella; D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: B cells; Bacterial infection; Clonal expansion; Germinal centers; Immunity