Sphingosine 1-phosphate regulates the egress of IgA plasmablasts from Peyer's patches for intestinal IgA responses.
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.
Gohda
Masashi
M
Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Kunisawa
Jun
J
Miura
Fumi
F
Kagiyama
Yuki
Y
Kurashima
Yosuke
Y
Higuchi
Morio
M
Ishikawa
Izumi
I
Ogahara
Ikuko
I
Kiyono
Hiroshi
H
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
D007070:Immunoglobulin A; D007166:Immunosuppressive Agents; D008246:Lysophospholipids; D011409:Propylene Glycols; C060506:sphingosine 1-phosphate; D010047:Ovalbumin; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine