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Signaling protein SWAP-70 is required for efficient B cell homing to lymphoid organs

Nature Immunology volume 7, pages 827–834 (2006)Cite this article

Abstract

The migration of B cells into secondary lymphoid organs is required for the generation of an effective immune response. Here we analyzed the involvement of SWAP-70, a Rac-interacting protein involved in actin rearrangement, in B cell entry into lymph nodes. We noted reduced migration of Swap70−/− B cells into lymph nodes in vivo. Swap70−/− B cells rolled and adhered, yet accumulated in lymph node high endothelial venules. This defect was not due to impaired integrin expression or chemotaxis. Instead, Swap70−/− B cells aberrantly regulated integrin-mediated adhesion. During attachment, Swap70−/− B cells showed defective polarization and did not form uropods or stabilize lamellipodia at a defined region. Thus, SWAP-70 selectively regulates processes essential for B cell entry into lymph nodes.

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Figure 1: Inflammation-induced accumulation of Swap70−/− B cells in lymph nodes.
Figure 2: Migration of Swap70−/− B cells to lymph nodes.
Figure 3: Integrin-mediated adhesion of Swap70−/− B cells.
Figure 4: Polarization of Swap70−/− B cells.
Figure 5: Adhesion of Swap70−/− B cells.
Figure 6: Lamellipodia formation.
Figure 7: B cell accumulation in HEVs.

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Acknowledgements

We thank L. Quemeneur for discussions, and A. Berg and M. Chopin for help. Supported by the National Institutes of Health (AI49470 to R.J.) and the Deutsche Forschungsgemeinschaft (SFB605 to R.J.).

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Authors and Affiliations

  1. Institute of Physiological Chemistry, Dresden University of Technology, Dresden, 01307, Germany

    Glen Pearce & Rolf Jessberger

  2. Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, 10029, New York, USA

    Veronique Angeli, Gwendalyn J Randolph & Rolf Jessberger

  3. Center for Blood Research, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Tobias Junt & Ulrich von Andrian

  4. Institute of Physiology, Dresden University of Technology, Dresden, 01307, Germany

    Hans-Joachim Schnittler

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Correspondence to Rolf Jessberger.

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Supplementary information

Supplementary Fig. 1

Inflammation-induced migration of B cells into the peritoneum. (PDF 207 kb)

Supplementary Fig. 2

Flow cytometric analysis of integrin and chemokine receptor expression on purified B cells. (PDF 692 kb)

Supplementary Fig. 3

Actin polymerization and Rac-1 activity and localization. (PDF 531 kb)

Supplementary Video 1

WT B cells moving on an anti-CD44 coated surface. Images were collected every 10 sec for 20 min after a 25 min attachment period. (MOV 3624 kb)

Supplementary Video 2

Swap70−/− B cells moving on an anti-CD44 coated surface. Images were collected every 10 sec for 20 min after a 25 min attachment period. (MOV 3100 kb)

Supplementary Methods (PDF 73 kb)

Supplementary Note (PDF 66 kb)

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Pearce, G., Angeli, V., Randolph, G. et al. Signaling protein SWAP-70 is required for efficient B cell homing to lymphoid organs. Nat Immunol 7, 827–834 (2006). https://doi.org/10.1038/ni1365

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