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The opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling

Author

Listed:
  • Kerry Tedford

    (Otto-von-Guericke University Magdeburg)

  • Michael Steiner

    (Otto-von-Guericke University Magdeburg)

  • Stanislav Koshutin

    (Otto-von-Guericke University Magdeburg)

  • Karin Richter

    (Otto-von-Guericke University Magdeburg)

  • Laura Tech

    (Otto-von-Guericke University Magdeburg
    Charite Universitätsmedizin)

  • Yannik Eggers

    (Otto-von-Guericke University Magdeburg)

  • Inga Jansing

    (Otto-von-Guericke University Magdeburg)

  • Kerstin Schilling

    (Otto-von-Guericke University Magdeburg)

  • Anja Erika Hauser

    (Charite Universitätsmedizin)

  • Mark Korthals

    (Otto-von-Guericke University Magdeburg)

  • Klaus-Dieter Fischer

    (Otto-von-Guericke University Magdeburg)

Abstract

Splenic marginal zone B cells (MZB) shuttle between the blood-filled marginal zone for antigen collection and the follicle for antigen delivery. However, it is unclear how MZBs migrate directionally from the marginal zone to the follicle. Here, we show that murine MZBs migrate up shear flow via the LFA-1 (αLβ2) integrin ligand ICAM-1, but adhere or migrate down the flow via the VLA-4 integrin (α4β1) ligand VCAM-1. MZBs lacking Arhgef6 (Pak-interacting exchange factor (αPIX)) or functional LFA-1 are impaired in shuttling due to mislocalization toward the VCAM-1-rich red pulp. Sphingosine-1-phosphate (S1P) signaling through the S1PR3 receptor inhibits MZB migration up the flow, and deletion of S1pr3 in Arhgef6 −/− mice rescues mislocalized MZBs. These findings establish shear flow as a directional cue for MZB migration to the follicle, and define S1PR3 and VCAM-1 as counteracting forces that inhibit this migration.

Suggested Citation

  • Kerry Tedford & Michael Steiner & Stanislav Koshutin & Karin Richter & Laura Tech & Yannik Eggers & Inga Jansing & Kerstin Schilling & Anja Erika Hauser & Mark Korthals & Klaus-Dieter Fischer, 2017. "The opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02482-4
    DOI: 10.1038/s41467-017-02482-4
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