Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent intestinal IgA production.
Sphingosine 1-phosphate (S1P) is known to play a pivotal role in the regulation of lymphocyte emigration from organized lymphoid tissues such as the peripheral lymph nodes and thymus, but its immunologic role in unorganized and diffused tissues remains to be elucidated. Here we show that the trafficking of peritoneal B cells is principally regulated by S1P. All peritoneal B cells including B1a, B1b, and B2 B cells express comparable levels of the type 1 S1P receptor. Thus, treatment with FTY720, an S1P receptor modulator, caused the rapid disappearance of peritoneal B cells by inhibiting both their emigration from parathymic lymph nodes and their recirculation from the blood into the peritoneal cavity without affecting their progenitor populations. These changes did not affect natural plasma antibody production or phosphorylcholine (PC)-specific antibody production in serum after peritoneal immunization with heat-killed Streptococcal pneumoniae (R36A). However, FTY720 dramatically reduced peritoneal B cell-derived natural intestinal secretory IgA production without affecting the expression of J-chain and polyimmunoglobulin receptors. Additionally, FTY720 impaired the generation of PC-specific fecal IgA responses after oral immunization with R36A. These findings point to a pivotal role for S1P in connecting peritoneal B cells with intestinal B-cell immunity.
Kunisawa
Jun
J
Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Kurashima
Yosuke
Y
Gohda
Masashi
M
Higuchi
Morio
M
Ishikawa
Izumi
I
Miura
Fumi
F
Ogahara
Ikuko
I
Kiyono
Hiroshi
H
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000096:biosynthesis / Q000276:immunology; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001428:Bacterial Vaccines / Q000276:immunology / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D005260:Female; D000068876:Fingolimod Hydrochloride; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism; D007144:Immunoglobulin J-Chains / Q000096:biosynthesis / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007421:Intestine, Small / Q000276:immunology* / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D010529:Peritoneal Cavity; D011409:Propylene Glycols / Q000494:pharmacology*; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000096:biosynthesis / Q000276:immunology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000276:immunology; D014611:Vaccination
D017152:Antibodies, Antiphospholipid; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D007144:Immunoglobulin J-Chains; D007166:Immunosuppressive Agents; D008246:Lysophospholipids; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine