Distinct roles for Peyer's patch B cells for induction of antigen-specific IgA antibody responses in mice administered oral recombinant Salmonella

Tomomi Hashizume-Takizawa*, Naoko Shibata, Yosuke Kurashima, Hiroshi Kiyono, Tomoko Kurita-Ochiai, Kohtaro Fujihashi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Our previous study demonstrated an indispensable role of Peyer's patches (PPs) for the induction of antigen-specific secretory (S)IgA antibody responses after oral immunization with recombinant Salmonella expressing fragment C of tetanus toxin (rSalmonella-Tox C). In this study, we defined the PP lymphoid structures and immune cells required for the induction of mucosal SIgA antibody responses. Adoptive transfer of mononuclear cells (MNCs) from PPs into PP-deficient (PP-null) mice failed to elicit tetanus toxoid (TT)-specific mucosal immunity. However, when the same PP MNCs were transferred into lethally irradiated PP-normal recipient mice, PP MNCs preferentially emigrated to recipient PPs, leading to PP lymphoid structures and TT-specific SIgA antibody responses. Significantly reduced numbers of TT-specific IgA antibody-forming cells were detected in the mesenteric lymph nodes (MLNs) and intestinal lamina propria of mice when surface expression of the sphingosine 1-phosphate receptor on lymphocytes was inhibited by its agonist FTY720. However, FTY720 treatment did not alter dendritic cell migration or Salmonella dissemination into these tissues. When rSalmonella-Tox C-stimulated CD4+ T cells isolated from PPs, MLNs and the spleen were co-cultured with B cells from these tissues, significantly increased levels of TT-specific IgA antibody responses were exclusively induced in cultures containing PP B cells. Furthermore, surface IgA+ PP B cells produced TT-specific IgA antibody responses in vitro. These findings suggest that PP lymphoid structures and surface IgA+ PP B cells are essential elements for the induction of antigen-specific intestinal SIgA antibody responses to oral Salmonella.

Original languageEnglish
Pages (from-to)531-541
Number of pages11
JournalInternational Immunology
Volume31
Issue number8
DOIs
Publication statusPublished - 2019 Aug 1

Keywords

  • gut-associated lymphoid tissue
  • homing
  • mucosal immunity
  • oral immunization
  • secretory IgA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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