Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone.
The factors directing marginal zone B cells to the splenic marginal zone are not well understood. Here we report that FTY720, a drug that targets sphingosine 1-phosphate (S1P) receptors, induced marginal zone B cell migration into follicles. Marginal zone B cells expressed S1P receptors 1 and 3 (S1P(1) and S1P(3), respectively). Using gene-targeted mice, we show that S1P(1) but not S1P(3) was required for localization in the marginal zone. In mice lacking the chemokine CXCL13, S1P(1)-deficient marginal zone B cells reacquired a marginal zone distribution. Exposure to lipopolysaccharide or antigen caused marginal zone B cells to downregulate S1P(1) and S1P(3) and to migrate into the splenic white pulp. These data suggest that marginal zone B cell localization to the marginal zone depends on responsiveness to the blood lysophospholipid S1P, with S1P(1) signaling overcoming the recruiting activity of CXCL13.
Cinamon
Guy
G
Howard Hughes Medical Institute, Department of Microbiology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0414, USA.
Matloubian
Mehrdad
M
Lesneski
Matthew J
MJ
Xu
Ying
Y
Low
Caroline
C
Lu
Theresa
T
Proia
Richard L
RL
Cyster
Jason G
JG
D000818:Animals; D000941:Antigens / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000172:deficiency / Q000235:genetics; D002678:Chimera / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects; D000068876:Fingolimod Hydrochloride; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011409:Propylene Glycols / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D049312:Receptors, Lysophospholipid; D013110:Sphingosine / Q000031:analogs & derivatives; D013154:Spleen / Q000166:cytology* / Q000276:immunology
D000941:Antigens; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D008070:Lipopolysaccharides; D011409:Propylene Glycols; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine