Fc receptor–like 1 intrinsically recruits c-Abl to enhance B cell activation and function

Abstract

B cell activation is regulated by the stimulatory or inhibitory co-receptors of B cell receptors (BCRs). Here, we investigated the signaling mechanism of Fc receptor-like 1 (FcRL1), a newly identified BCR co-receptor. FcRL1 was passively recruited into B cell immunological synapses upon BCR engagement in the absence of FcRL1 cross-linking, suggesting that FcRL1 may intrinsically regulate B cell activation and function. BCR cross-linking alone led to the phosphorylation of the intracellular Y281ENV motif of FcRL1 to provide a docking site for c-Abl, an SH2 domain-containing kinase. The FcRL1 and c-Abl signaling module, in turn, potently augmented B cell activation and proliferation. FcRL1-deficient mice exhibited markedly impaired formation of extrafollicular plasmablasts and germinal centers, along with decreased antibody production upon antigen stimulation. These findings reveal a critical BCR signal-enhancing function of FcRL1 through its intrinsic recruitment to B cell immunological synapses and subsequent recruitment of c-Abl upon BCR cross-linking.

A novel prognostic prediction model based on seven immune-related RNAs for predicting overall survival of patients in early cervical squamous cell carcinoma

“…Fc receptor-like 1 ( FCRL1 ) is a novel B cell receptor (BCR) co-receptor. Zhao et al ( 38 ) revealed a vital BCR signal enhancement role of FCRL1 via its internal B cell immune synapse recruitment and subsequent c-Abl recruitment on BCR cross-linking. Furthermore, KEGG and GO analyses expressed that the genes were enriched in the immune response pathway.…”

Immune Features of COVID-19 Convalescent Individuals Revealed by a Single-cell RNA Sequencing

“…It is noteworthy that FcRL1 was upregulated in Memory B only from severe convalescent COVID-19 patients. There is a study shows that FcRL1 enhances B cell activation and function [41]. In another panel of genes relevant to humoral immune response, we found two molecules S100A8 and S100A9 upregulated in Plasma B only from severe subjects.…”

“…However, another study showed that within 6 to 10 weeks of SARS-COV-2 infection, the level of (RBD)-speci c IgG speci c to the receptor domain decreased [71], indicating that B lymphocytes have dual functions during the recovery phase. A recent study reported key roles of Fc receptor-like 1 (FCRL1), a newly identi ed BCR co-receptor speci cally expressed on the surface of B cells, in antibody production unveiled by experiment showing that FcRL1-de cient mice exhibited markedly impaired formation of extrafollicular plasmablasts and germinal centers, along with decreased antibody production upon antigen stimulation [41]. In our study, we found that the expression of FCRL1, a gene related to B cell activation, was signi cantly increased in patients with moderate recovery, suggesting that B cell function was activated.…”

Immune features of COVID-19 convalescent individuals revealed by a single-cell RNA sequencing

“…It is noteworthy that FcRL1 was upregulated in Memory B only from severe convalescent COVID-19 patients. A study showed that FcRL1 enhances B cell activation and function [41] . In another panel of genes relevant to humoral immune response, we found two molecules S100A8 and S100A9 upregulated in Plasma B only from severe subjects.…”