期刊
BLOOD
卷 108, 期 13, 页码 4086-4093出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-05-025338
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资金
- NIAID NIH HHS [AI-46405, T32 AI-49822, T32 AI049822, R01 AI046405, R01 AI065773] Funding Source: Medline
BCR-mediated antigen processing occurs at immunologically relevant antigen concentrations and hinges on the trafficking of antigen-BCR (Ag-BCR) complexes to class II-containing multivesicular bodies (MVBs) termed MIICs. However, the molecular mechanism underlying the trafficking of Ag-BCR complexes to and within MIICs is not well understood. In contrast, the trafficking of the epidermal growth factor receptor (EGFR) to and within MVBs occurs via a well-characterized ubiquitin-dependent mechanism, which is blocked by acute inhibition of proteasome activity. Using a highly characterized antigen-specific model system, it was determined that the immunoglobulin heavy chain subunit of the IgM BCR of normal (ie, nontransformed) B cells is ubiquitinated. Moreover, acute inhibition of proteasome activity delays the formation of ubiquitinated ligand-BCR complexes, alters the intracellular trafficking of internalized Ag-BCR complexes, and selectively blocks the BCR-mediated processing and presentation of cognate antigen, without inhibiting the endocytosis, processing, and presentation of non-cognate antigen internalized by fluid-phase endocytosis. These results demonstrate that the trafficking of Ag-BCR complexes to and within MVB-like antigen processing compartments occurs via a molecular mechanism with similarities to that used by the EGFR, and establishes the EGFR as a paradigm for the further analysis of Ag-BCR trafficking to and within MIICs. (Blood. 2006;108:4086-4093) (c) 2006 by The American Society of Hematology.
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