Syk-dependent actin dynamics regulate endocytic trafficking and processing of antigens internalized through the B-cell receptor.
Antigen binding to the B-cell receptor (BCR) induces multiple signaling cascades that ultimately lead to B lymphocyte activation. In addition, the BCR regulates the key trafficking events that allow the antigen to reach endocytic compartments devoted to antigen processing, i.e., that are enriched for major histocompatibility factor class II (MHC II) and accessory molecules such as H2-DM. Here, we analyze the role in antigen processing and presentation of the tyrosine kinase Syk, which is activated upon BCR engagement. We show that convergence of MHC II- and H2-DM-containing compartments with the vesicles that transport BCR-uptaken antigens is impaired in cells lacking Syk activity. This defect in endocytic trafficking compromises the ability of Syk-deficient cells to form MHC II-peptide complexes from BCR-internalized antigens. Altered endocytic trafficking is associated to a failure of Syk-deficient cells to properly reorganize their actin cytoskeleton in response to BCR engagement. We propose that, by modulating the actin dynamics induced upon BCR stimulation, Syk regulates the positioning and transport of the vesicles that carry the molecules required for antigen processing and presentation.
Le Roux
Delphine
D
Institut National de la Santé et de la Recherche Médicale U653, Institut Curie, 75005, Paris, France.
Lankar
Danielle
D
Yuseff
Maria-Isabel
MI
Vascotto
Fulvia
F
Yokozeki
Takeaki
T
Faure-André
Gabrielle
G
Mougneau
Evelyne
E
Glaichenhaus
Nicolas
N
Manoury
Bénédicte
B
Bonnerot
Christian
C
Lennon-Duménil
Ana-Maria
AM
D000199:Actins / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism; D004705:Endocytosis; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000378:metabolism*; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D010455:Peptides / Q000378:metabolism; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000378:metabolism* / Q000648:ultrastructure; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D000072377:Syk Kinase
D000199:Actins; D000949:Histocompatibility Antigens Class II; D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse