Chapter

Sphingosine-1-Phosphate Signaling in Immunology and Infectious Diseases

Volume 378 of the series Current Topics in Microbiology and Immunology pp 107-128

Date:

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

  • Tal I. ArnonAffiliated withHoward Hughes Medical Institute and Department of Microbiology and Immunology, University of California San FranciscoThe Kennedy Institute of Rheumatology, University of Oxford Email author 
  • , Jason G. CysterAffiliated withHoward Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco Email author 

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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.