| First Author | DeLuca JM | Year | 2021 |
| Journal | J Immunol | Volume | 207 |
| Issue | 11 | Pages | 2688-2698 |
| PubMed ID | 34697226 | Mgi Jnum | J:317170 |
| Mgi Id | MGI:6849873 | Doi | 10.4049/jimmunol.2100218 |
| Citation | DeLuca JM, et al. (2021) FCRL1 Regulates B Cell Receptor-Induced ERK Activation through GRB2. J Immunol 207(11):2688-2698 |
| abstractText | 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. |
