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Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone

Nature Immunology volume 5, pages 713–720 (2004)Cite this article

Abstract

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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Figure 1: FTY720 treatment causes rapid and reversible marginal zone B cell relocalization into lymphoid follicles.
Figure 2: Marginal zone B cells have higher expression of S1P1 and S1P3 than do follicular B cells and show robust chemotactic responsiveness to S1P.
Figure 3: S1P1-deficient fetal liver chimeras have normal numbers of marginal zone B cells, but these cells fail to lodge in the marginal zone.
Figure 4: S1P chemotactic responsiveness of S1P1- and S1P3-deficient marginal zone B cells and marginal zone B cell distribution in S1P3-deficient mice.
Figure 5: In CXCL13-deficient mice, FTY720 fails to cause marginal zone B cell displacement and S1P1-deficient marginal zone B cells localize in the marginal zone.
Figure 6: LPS and antigen exposure cause downregulation of S1P1 and S1P3 and reduced S1P responsiveness.

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Acknowledgements

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.

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  1. Theresa Lu

    Present address: Hospital for Special Surgery, Caspary Research Building 2nd Floor, 535 East 70th Street, New York, New York, 10021, USA

Authors and Affiliations

  1. Howard Hughes Medical Institute, University of California San Francisco, 513 Parnassus Avenue, San Francisco, 94143-0414, California, USA

    Guy Cinamon, Mehrdad Matloubian, Matthew J Lesneski, Ying Xu, Caroline Low, Theresa Lu & Jason G Cyster

  2. Departments of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, 94143-0414, California, USA

    Guy Cinamon, Mehrdad Matloubian, Matthew J Lesneski, Ying Xu, Caroline Low, Theresa Lu & Jason G Cyster

  3. Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, 20892-1821, Maryland, USA

    Richard L Proia

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Correspondence to Jason G Cyster.

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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). https://doi.org/10.1038/ni1083

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