Journal article
Igβ ubiquitination activates PI3K signals required for endosomal sorting
The Journal of experimental medicine, Vol.214(12), pp.3775-3790
12/04/2017
DOI: 10.1084/jem.20161868
PMCID: PMC5716028
PMID: 29141870
Abstract
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.
Details
- Title: Subtitle
- Igβ ubiquitination activates PI3K signals required for endosomal sorting
- Creators
- Margaret Veselits - Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, Departments of Medicine and Pathology, University of Chicago, Chicago, ILAzusa Tanaka - Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, Departments of Medicine and Pathology, University of Chicago, Chicago, ILYaoqing Chen - Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, Departments of Medicine and Pathology, University of Chicago, Chicago, ILKeith Hamel - Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, Departments of Medicine and Pathology, University of Chicago, Chicago, ILMalay Mandal - Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, Departments of Medicine and Pathology, University of Chicago, Chicago, ILMatheswaran Kandasamy - Department of Microbiology, University of Chicago, Chicago, ILBalaji Manicassamy - Department of Microbiology, University of Chicago, Chicago, ILShannon K O'Neill - Division of Infectious Diseases, University of Colorado, Aurora, COPatrick Wilson - Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, Departments of Medicine and Pathology, University of Chicago, Chicago, ILRoger Sciammas - Center for Comparative Medicine, University of California, Davis, Davis, CAMarcus R Clark - Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, Departments of Medicine and Pathology, University of Chicago, Chicago, IL mclark@uchicago.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.214(12), pp.3775-3790
- DOI
- 10.1084/jem.20161868
- PMID
- 29141870
- PMCID
- PMC5716028
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Grant note
- R01 GM101090 / NIGMS NIH HHS R01 GM088847 / NIGMS NIH HHS
- Language
- English
- Date published
- 12/04/2017
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083289602771
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