B cell antigen receptor endocytosis and antigen presentation to T cells require Vav and dynamin.
Antigen binding to the B cell antigen receptor (BCR) initiates an array of signaling events. These include endocytosis of ligand-receptor complexes via clathrin-coated pits, trafficking of the internalized ligand to lysosomes, degradation of the associated proteins to peptides, and peptide presentation on nascent major histocompatibility complex class II to T cells. The signal transduction events supporting BCR internalization are not well understood. We have identified a pathway supporting BCR internalization that includes the Vav1 and/or Vav3 isoforms and the GTPase dynamin. Vav1 and -3 are not required for B cell development and maturation, nor for a variety of BCR-induced signaling events nor for BCR signaling leading to major histocompatibility complex class II and CD80 expression, but Vav1 and/or -3 are absolutely required for BCR endocytosis and BCR-induced Rac-GTP loading. This is the first demonstration of a link between Vav and Rac in BCR internalization leading to antigen presentation to T cells.
Malhotra
Shikha
S
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Kovats
Susan
S
Zhang
Weiguo
W
Coggeshall
K Mark
KM
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D022163:Clathrin-Coated Vesicles / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D034281:Dynamins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D018122:B7-1 Antigen; D000949:Histocompatibility Antigens Class II; D020033:Protein Isoforms; D051567:Proto-Oncogene Proteins c-vav; D011947:Receptors, Antigen, B-Cell; C496619:Vav1 protein, mouse; C496622:Vav3 protein, mouse; D020744:rac GTP-Binding Proteins; D034281:Dynamins