Igβ ubiquitination activates PI3K signals required for endosomal sorting

Margaret Veselits, Azusa Tanaka, Yaoqing Chen, Keith Hamel, Malay Mandal, Matheswaran Kandasamy, Balaji Manicassamy, Shannon K. O'Neill, Patrick Wilson, Roger Sciammas, Marcus R. Clark

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


A wealth of in vitro data has demonstrated a central role for receptor ubiquitination in endocytic sorting. However, how receptor ubiquitination functions in vivo is poorly understood. Herein, we report that ablation of B cell antigen receptor ubiquitination in vivo uncouples the receptor from CD19 phosphorylation and phosphatidylinositol 3-kinase (PI3K) signals. These signals are necessary and sufficient for accumulating phosphatidylinositol (3,4,5)-trisphosphate (PIP3) on B cell receptor- containing early endosomes and proper sorting into the MHC class II antigen-presenting compartment (MIIC). Surprisingly, MIIC targeting is dispensable for T cell-dependent immunity. Rather, it is critical for activating endosomal toll-like receptors and antiviral humoral immunity. These findings demonstrate a novel mechanism of receptor endosomal signaling required for specific peripheral immune responses.

Original languageEnglish
Pages (from-to)3775-3790
Number of pages16
JournalJournal of Experimental Medicine
Issue number12
StatePublished - 1 Dec 2017
Externally publishedYes


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