Nature Immunology
5, 713 - 720 (2004)
Published online: 6 June 2004; | doi:10.1038/ni1083
Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zoneGuy Cinamon1, 2, Mehrdad Matloubian1, 2, Matthew J Lesneski1, 2, Ying Xu1, 2, Caroline Low1, 2, Theresa Lu1, 2, 4, Richard L Proia3
& Jason G Cyster1, 21
Howard Hughes Medical Institute, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0414, USA. 2
Departments of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0414, USA. 3
Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1821, USA. 4
Present address: Hospital for Special Surgery, Caspary Research Building 2nd Floor, 535 East 70th Street, New York, New York 10021, USA.
Correspondence should be addressed to Jason G Cyster cyster@itsa.ucsf.eduThe 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 (S1P1 and S1P3, respectively). Using gene-targeted mice, we show that S1P1 but not S1P3 was required for localization in the marginal zone. In mice lacking the chemokine CXCL13, S1P1-deficient marginal zone B cells reacquired a marginal zone distribution. Exposure to lipopolysaccharide or antigen caused marginal zone B cells to downregulate S1P1 and S1P3 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 S1P1 signaling overcoming the recruiting activity of CXCL13.
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