1. FCRL1 Regulates B Cell Receptor–Induced ERK Activation through GRB2
- Author
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Maegan K. Murphy, Xin Wang, Jenna M DeLuca, and Timothy J. Wilson
- Subjects
MAPK/ERK pathway ,biology ,Chemistry ,Immunology ,B-cell receptor ,Regulator ,Cell biology ,medicine.anatomical_structure ,In vivo ,Calcium flux ,biology.protein ,medicine ,Immunology and Allergy ,GRB2 ,B cell ,Homeostasis - Abstract
Regulation of BCR signaling has important consequences for generating effective Ab responses to pathogens and preventing production of autoreactive B cells during development. Currently defined functions of Fc receptor-like (FCRL) 1 include positive regulation of BCR-induced calcium flux, proliferation, and Ab production; however, the mechanistic basis of FCRL1 signaling and its contributions to B cell development remain undefined. Molecular characterization of FCRL1 signaling shows phosphotyrosine-dependent associations with GRB2, GRAP, SHIP-1, and SOS1, all of which can profoundly influence MAPK signaling. In contrast with previous characterizations of FCRL1 as a strictly activating receptor, we discover a role for FCRL1 in suppressing ERK activation under homeostatic and BCR-stimulated conditions in a GRB2-dependent manner. Our analysis of B cells in Fcrl1−/− mice shows that ERK suppression by FCRL1 is associated with a restriction in the number of cells surviving splenic maturation in vivo. The capacity of FCRL1 to modulate ERK activation presents a potential for FCRL1 to be a regulator of peripheral B cell tolerance, homeostasis, and activation.
- Published
- 2021