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Btk Regulates B Cell Receptor-Mediated Antigen Processing and Presentation by Controlling Actin Cytoskeleton Dynamics in B Cells

Shruti Sharma, Gregory Orlowski and Wenxia Song
J Immunol January 1, 2009, 182 (1) 329-339; DOI: https://doi.org/10.4049/jimmunol.182.1.329
Shruti Sharma
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742
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Gregory Orlowski
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742
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Wenxia Song
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742
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Abstract

The high efficiency of Ag processing and presentation by B cells requires Ag-induced BCR signaling and actin cytoskeleton reorganization, although the underlying mechanism for such requirements remains elusive. In this study, we identify Bruton’s tyrosine kinase (Btk) as a linker connecting BCR signaling to actin dynamics and the Ag transport pathway. Using xid mice and a Btk inhibitor, we show that BCR engagement increases actin polymerization and Wiskott-Aldrich syndrome protein activation in a Btk-dependent manner. Concurrently, we observe Btk-dependent increases in the levels of phosphatidylinositide-4,5-bisphosphate and phosphorylated Vav upon BCR engagement. The rate of BCR internalization, its movement to late endosomes, and efficiency of BCR-mediated Ag processing and presentation are significantly reduced in both xid and Btk inhibitor-treated B cells. Thus, Btk regulates actin dynamics and Ag transport by activating Wiskott-Aldrich syndrome protein via Vav and phosphatidylinositides. This represents a novel mechanism by which BCR-mediated signaling regulates BCR-mediated Ag processing and presentation.

  • Received June 2, 2008.
  • Accepted October 28, 2008.
  • Copyright © 2009 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 182 (1)
The Journal of Immunology
Vol. 182, Issue 1
1 Jan 2009
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Btk Regulates B Cell Receptor-Mediated Antigen Processing and Presentation by Controlling Actin Cytoskeleton Dynamics in B Cells
Shruti Sharma, Gregory Orlowski, Wenxia Song
The Journal of Immunology January 1, 2009, 182 (1) 329-339; DOI: 10.4049/jimmunol.182.1.329

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Btk Regulates B Cell Receptor-Mediated Antigen Processing and Presentation by Controlling Actin Cytoskeleton Dynamics in B Cells
Shruti Sharma, Gregory Orlowski, Wenxia Song
The Journal of Immunology January 1, 2009, 182 (1) 329-339; DOI: 10.4049/jimmunol.182.1.329
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