Direct visualization of endogenous Salmonella-specific B cells reveals a marked delay in clonal expansion and germinal center development

Eur J Immunol. 2015 Feb;45(2):428-41. doi: 10.1002/eji.201444540. Epub 2014 Nov 20.

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.

Keywords: B cells; Bacterial infection; Clonal expansion; Germinal centers; Immunity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / microbiology
  • B-Lymphocytes / pathology
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / microbiology
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Proliferation
  • Clone Cells
  • Flow Cytometry / methods
  • Gene Expression
  • Germinal Center / immunology*
  • Germinal Center / microbiology
  • Germinal Center / pathology
  • Host-Pathogen Interactions
  • Immunization
  • Immunophenotyping
  • Lipopolysaccharides / administration & dosage
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics*
  • Membrane Proteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / immunology
  • Ovalbumin / administration & dosage
  • Ovalbumin / chemistry
  • Ovalbumin / immunology
  • Salmonella typhimurium / immunology*
  • Time Factors

Substances

  • Bacterial Proteins
  • Lipopolysaccharides
  • Membrane Proteins
  • SPI-2 protein, Salmonella
  • Ovalbumin
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse