TY - JOUR
T1 - Igβ ubiquitination activates PI3K signals required for endosomal sorting
AU - Veselits, Margaret
AU - Tanaka, Azusa
AU - Chen, Yaoqing
AU - Hamel, Keith
AU - Mandal, Malay
AU - Kandasamy, Matheswaran
AU - Manicassamy, Balaji
AU - O'Neill, Shannon K.
AU - Wilson, Patrick
AU - Sciammas, Roger
AU - Clark, Marcus R.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20161868
DO - 10.1084/jem.20161868
M3 - Article
C2 - 29141870
AN - SCOPUS:85036517240
VL - 214
SP - 3775
EP - 3790
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 12
ER -