Btk regulates B cell receptor-mediated antigen processing and presentation by controlling actin cytoskeleton dynamics in B cells.
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.
Sharma
Shruti
S
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Orlowski
Gregory
G
Song
Wenxia
W
D000199:Actins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D021381:Protein Transport / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D051316:Wiskott-Aldrich Syndrome Protein / Q000502:physiology
D000199:Actins; D003598:Cytoskeletal Proteins; D011947:Receptors, Antigen, B-Cell; C495768:Was protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse