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Follicular shuttling of marginal zone B cells facilitates antigen transport

Nature Immunology volume 9, pages 54–62 (2008)Cite this article

Abstract

The splenic marginal zone is a site of blood flow, and the specialized B cell population that inhabits this compartment has been linked to the capture and follicular delivery of blood-borne antigens. However, the mechanism of this antigen transport has remained unknown. Here we show that marginal zone B cells were not confined to the marginal zone but continuously shuttled between the marginal zone and follicular areas, such that many of the cells visited a follicle every few hours. Migration to the follicle required the chemokine receptor CXCR5, whereas return to the marginal zone was promoted by the sphingosine 1-phosphate receptors S1P1 and S1P3. Treatment with an S1P1 antagonist caused displacement of marginal zone B cells from the marginal zone. Marginal zone–follicle shuttling of marginal zone B cells provides an efficient mechanism for systemic antigen capture and delivery to follicular dendritic cells.

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Figure 1: Treatment for 3 h with the S1P1 antagonist VPC44116 causes displacement of marginal zone B cells into follicles.
Figure 2: Positioning of marginal zone B cells in the marginal zone is required for efficient binding of blood-borne antigen.
Figure 3: Positioning of marginal zone B cells in the marginal zone is required for efficient delivery of blood-borne immune complexes to FDCs, and expression of CXCR5 by B cells is necessary for deposition of TNP-Ficoll on FDCs.
Figure 4: In vivo antibody labeling provides evidence for marginal zone-follicle shuttling of marginal zone B cells in the absence of immunization.
Figure 5: Accumulation of FDC-M2 on marginal zone B cells of CXCR5-deficient mice.
Figure 6: Balance of S1P1 and CXCR5 responsiveness and S1P3 control marginal zone B cell shuttling.

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Acknowledgements

We thank J. Pereira for sharing in vivo labeling techniques; J. An and Y. Xu for technical help; R. Proia (National Institute of Diabetes and Digestive and Kidney Diseases) for S1P1- and S1P3-deficient mice; M. Lipp (Max Delbrück Center of Molecular Medicine;) and R. Forster (Hannover Medical School) for CXCR5-deficient mice; X. Wu and J. Atkinson (Washington University School of Medicine) for Cr2−/− mice; K. Rajewsky (The CBR Institute for Biomedical Research, Harvard Medical School) for CD19-Cre mice; K. Lynch and T. MacDonald (University of Virginia Medical Center) for VPC44116; C. Allen for help with the LSRII; L. Shiow for discussions; and T. Phan for comments on the manuscript. Supported by the Howard Hughes Medical Institute (G.C. and J.G.C.) and the National Institutes of Health (AI40098).

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  1. Frank W Foss Jr

    Present address: Present address: Department of Chemistry, Columbia University, New York, New York 10027, USA.,

Authors and Affiliations

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

    Guy Cinamon, Marcus A Zachariah, Olivia M Lam & Jason G Cyster

  2. Department of Chemistry, University of Virginia, Charlottesville, 22904, Virginia, USA

    Frank W Foss Jr

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Contributions

G.C. and J.G.C. designed and conceptualized the research; G.C. did the experiments; M.A.Z. was involved in several in vivo labeling experiments; O.M.L. helped with animal management and genotyping; F.W.F. generated VPC44116; and G.C. and J.G.C. analyzed the data and prepared the manuscript.

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Correspondence to Jason G Cyster.

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Cinamon, G., Zachariah, M., Lam, O. et al. Follicular shuttling of marginal zone B cells facilitates antigen transport. Nat Immunol 9, 54–62 (2008). https://doi.org/10.1038/ni1542

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