B Cell Antigen Receptor Endocytosis and Antigen Presentation to T Cells Require Vav and Dynamin

Abstract

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.