The transmembrane tyrosine of μ-heavy chain is required for BCR destabilization and entry of antigen into clathrin-coated vesicles

Abstract

The B cell antigen receptor (BCR) delivers antigen to the endocytic compartment and transduces signals that regulate the stability of the receptor complex. Previous studies showed that BCR-mediated signal transduction dissociates μ-heavy chain (μm) from Ig-α/ Ig-β, facilitating the delivery of antigen to clathrin-coated vesicles (CCVs). Herein, we demonstrate that the dissociation of Ig-α/Ig-β from μm requires tyrosine-587 of the μm transmembrane domain. Receptors expressing a mutation at tyrosine-587 (Y587F) transduced signals that were comparable to wild type, yet they failed to dissociate μm from Ig-α/Ig-β. Further, receptors harboring the Y587F mutation failed to associate with CCVs, resulting in diminished antigen in the lysosome-associated membrane protein-1 (LAMP-1+) compartment and severely impaired antigen presentation, indicating that endocytosis through CCVs is required for antigen presentation. Thus, the transmembrane tyrosine of μm mediates destabilization of the BCR complex, facilitating antigen processing by promoting the association of antigen with CCVs. © The Japanese Society for Immunology. 2007. All rights reserved.