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

Int Immunol. 2007 Dec;19(12):1403-12. doi: 10.1093/intimm/dxm110. Epub 2007 Nov 1.

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 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / ultrastructure
  • Cell Line
  • Clathrin-Coated Vesicles / genetics
  • Clathrin-Coated Vesicles / immunology*
  • Clathrin-Coated Vesicles / metabolism
  • Clathrin-Coated Vesicles / ultrastructure
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology*
  • Immunoglobulin Heavy Chains / metabolism
  • Lysosomal Membrane Proteins / analysis
  • Mice
  • Microscopy, Electron, Transmission
  • Mutation
  • Receptors, Antigen, B-Cell / immunology*
  • Signal Transduction
  • Tyrosine / genetics
  • Tyrosine / immunology
  • Tyrosine / metabolism*

Substances

  • Antigens
  • Immunoglobulin Heavy Chains
  • Lamp1 protein, mouse
  • Lysosomal Membrane Proteins
  • Receptors, Antigen, B-Cell
  • Tyrosine