The transmembrane tyrosine of micro-heavy chain is required for BCR destabilization and entry of antigen into clathrin-coated vesicles.
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 micro-heavy chain (microm) from Ig-alpha/Ig-beta, facilitating the delivery of antigen to clathrin-coated vesicles (CCVs). Herein, we demonstrate that the dissociation of Ig-alpha/Ig-beta from microm requires tyrosine-587 of the microm transmembrane domain. Receptors expressing a mutation at tyrosine-587 (Y587F) transduced signals that were comparable to wild type, yet they failed to dissociate microm from Ig-alpha/Ig-beta. 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 mum mediates destabilization of the BCR complex, facilitating antigen processing by promoting the association of antigen with CCVs.
Kim
Jin Hyang
JH
Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Rutan
Jennifer A
JA
Vilen
Barbara J
BJ
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D002460:Cell Line; D022163:Clathrin-Coated Vesicles / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051907:Lysosomal Membrane Proteins / Q000032:analysis; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction; D014443:Tyrosine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D052118:Lysosomal-Associated Membrane Protein 1
D000941:Antigens; D007143:Immunoglobulin Heavy Chains; D051907:Lysosomal Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1