Ubiquitinylation of Igβ dictates the endocytic fate of the B cell antigen receptor

Miao Zhang, Margaret Veselits, Shannon O'Neill, Ping Hou, Alagarsamy L. Reddi, Ilana Berlin, Masato Ikeda, Piers D. Nash, Richard Longnecker, Hamid Band, Marcus R. Clark

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

In both infection and autoimmunity, the development of high-affinity Abs and memory requires B cells to efficiently capture and process Ags for presentation to cognate T cells. Although a great deal is known about how Ags are processed, the molecular mechanisms by which the BCR captures Ag for processing are still obscure. In this study, we demonstrate that the Igβ component of the BCR is diubiquitinylated and that this is dependent on the E3 ligase Itch. Itch-/- B lymphocytes manifest both a defect in ligand-induced BCR internalization and endocytic trafficking to late endosomal Ag-processing compartments. In contrast, analysis of ubiquitinylation-defective receptors demonstrated that the attachment of ubiquitins to Igβ is required for endosomal sorting and for the presentation of Ag to T cells, yet, ubiquitinylation is dispensable for receptor internalization. Membrane-bound Igμ was not detectably ubiquitinylated nor were the conserved lysines in the mu cytosolic tail required for trafficking to late endosomes. These results demonstrate that ubiquitinylation of a singular substrate, Igβ, is required for a specific receptor trafficking event. However, they also reveal that E3 ligases play a broader role in multiple processes that determine the fate of Ag-engaged BCR complexes.

Original languageEnglish (US)
Pages (from-to)4435-4443
Number of pages9
JournalJournal of Immunology
Volume179
Issue number7
DOIs
StatePublished - Oct 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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