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 (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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We thank V. Brinkmann for providing FTY720 (Novartis Institutes for Biomedical Research, Basel, Switzerland); D. Hargreaves for contributions to the early part of this project; M. Graeler for help with initial PCR analysis; and C. Lo for comments on the manuscript. Supported by Howard Hughes Medical Institute (G.C. and J.G.C.) and National Institutes of Health.
The authors declare no competing financial interests.
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Cinamon, G., Matloubian, M., Lesneski, M. et al. Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone. Nat Immunol 5, 713–720 (2004) doi:10.1038/ni1083
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