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Blood, Sphingosine-1-Phosphate and Lymphocyte Migration Dynamics in the Spleen

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Sphingosine-1-Phosphate Signaling in Immunology and Infectious Diseases

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 378))

Abstract

The spleen, the largest secondary lymphoid organ, has long been known to play important roles in immunity against blood-borne invaders. Yet how cells migrate within the spleen to ensure fast and effective responses is only now coming to light. Chemokines and oxysterols guide lymphocytes from sites of release at terminal arterioles into the lymphocyte-rich white pulp. Sphingosine-1-phosphate (S1P) and S1P-receptor-1 (S1PR1) promote lymphocyte egress from white to red pulp and back to circulation. Intravital two-photon microscopy has shown that marginal zone (MZ) B cells that are enriched between white and red pulps undergo continual oscillatory migration between the MZ and follicles, ferrying antigens. Cycles of G-protein-coupled receptor kinase-2 (GRK2) mediated S1PR1 desensitization and resensitization underlie this remarkable behavior. The findings discussed in this review have implications for understanding how splenic antibody and T-cell responses are mounted, how the immunosuppressant drug FTY720 (fingolimod) affects the spleen, and how cell shuttling behaviors contribute to immunity.

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Acknowledgments

We thank Cyster lab members for helpful discussions. T.I.A. was supported by a Jane Coffin Child’s fellowship and J.G.C. is an Investigator of the Howard Hughes Medical Institute. Work discussed in this review was supported by grants from the NIH.

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  1. Tal I. Arnon

    Present address: The Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK

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  1. Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, 94143, USA

    Tal I. Arnon & Jason G. Cyster

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  1. Tal I. Arnon
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  2. Jason G. Cyster
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Correspondence to Tal I. Arnon or Jason G. Cyster .

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  1. Department of Immunology and Microbial Sciiences, The Scripps Research Institute, La Jolla, California, USA

    Michael B. A. Oldstone

  2. Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA

    Hugh Rosen

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Arnon, T.I., Cyster, J.G. (2014). Blood, Sphingosine-1-Phosphate and Lymphocyte Migration Dynamics in the Spleen. In: Oldstone, M., Rosen, H. (eds) Sphingosine-1-Phosphate Signaling in Immunology and Infectious Diseases. Current Topics in Microbiology and Immunology, vol 378. Springer, Cham. https://doi.org/10.1007/978-3-319-05879-5_5

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