title: Sphingosine 1-phosphate regulates the egress of IgA plasmablasts from Peyer's patches for intestinal IgA responses.
abstract: 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.
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Gohda
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.forename: Fumi
authors.initials: F
authors.lastname: Miura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kagiyama
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kurashima
authors.forename: Morio
authors.initials: M
authors.lastname: Higuchi
authors.forename: Izumi
authors.initials: I
authors.lastname: Ishikawa
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ogahara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D000068876:Fingolimod Hydrochloride; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000276:immunology; D008246:Lysophospholipids / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010581:Peyer's Patches / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010950:Plasma Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D011409:Propylene Glycols / Q000008:administration & dosage / Q000494:pharmacology; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
chemical_list: D007070:Immunoglobulin A; D007166:Immunosuppressive Agents; D008246:Lysophospholipids; D011409:Propylene Glycols; C060506:sphingosine 1-phosphate; D010047:Ovalbumin; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine