Igβ ubiquitination activates PI3K signals required for endosomal sorting

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...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of experimental medicine 2017-12, Vol.214 (12), p.3775-3790
Main Authors: Veselits, Margaret, Tanaka, Azusa, Chen, Yaoqing, Hamel, Keith, Mandal, Malay, Kandasamy, Matheswaran, Manicassamy, Balaji, O'Neill, Shannon K, Wilson, Patrick, Sciammas, Roger, Clark, Marcus R
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Accumulation
Antigen processing
Antigens
B-cell receptor
CD19 antigen
Compartments
Endosomes
Humoral immunity
Immune response
Immune system
Immunity
Lymphocytes B
Lymphocytes T
Major histocompatibility complex
Membranes
Phosphatidylinositol 3,4,5-triphosphate
Phosphorylation
Proteins
Receptors
Signaling
T cell receptors
Toll-like receptors
Ubiquitination
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 (PIP ) 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.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20161868