Sphingosine 1-phosphate regulates the egress of IgA plasmablasts from Peyer's patches for intestinal IgA responses

Masashi Gohda, Jun Kunisawa, Fumi Miura, Yuki Kagiyama, Yosuke Kurashima, Morio Higuchi, Izumi Ishikawa, Ikuko Ogahara, Hiroshi Kiyono

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77 Citations (Scopus)


It is well established that Peyer's patches (PPs) are sites for the differentiation of IgA plasma cell precursors, but molecular and cellular mechanisms in their trafficking remain to be elucidated. In this study, we show that alterations in type 1 sphingosine 1-phosphate (S1P) receptor expression during B cell differentiation in the PPs control the emigration of IgA plasma cell precursors. Type 1 S1P receptor expression decreased during the differentiation of IgM+B220+ B cells to IgA +B220+ B cells, but recovered on IgA+B220 - plasmablasts for their emigration from the PPs. Thus, IgA +B220- plasmablasts migrated in response to S1P in vitro. Additionally, IgA+ plasmablasts selectively accumulated in lymphatic regions of PPs when S1P-mediated signaling was disrupted by FTY720 treatment. This accumulation of IgA+ plasmablasts in the PPs led to their reduction in the intestinal lamina propria and simultaneous impairment of Ag-specific intestinal IgA production against orally administered Ag. These findings suggest that S1P regulates the retention and emigration of PP B cells and plays key roles in the induction of intestinal IgA production..

Original languageEnglish
Pages (from-to)5335-5343
Number of pages9
JournalJournal of Immunology
Issue number8
Publication statusPublished - Apr 15 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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