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

Xingwang Zhao, Hengyi Xie, Meng Zhao, Asma Ahsan, Xinxin Li, Fei Wang, Junyang Yi, Zhiyong Yang, Chuan Wu, Indu Raman, Quan-zhen Li, Tae Jin Kim, Wanli Liu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbereaaw0315
JournalScience Advances
Volume5
Issue number7
DOIs
StatePublished - Jul 17 2019

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activation
synapses
phosphorylation
antigens
antibodies
stimulation
mice
modules

ASJC Scopus subject areas

  • General
  • Physics and Astronomy (miscellaneous)

Cite this

Zhao, X., Xie, H., Zhao, M., Ahsan, A., Li, X., Wang, F., ... Liu, W. (2019). Fc receptor–like 1 intrinsically recruits c-Abl to enhance B cell activation and function. Science Advances, 5(7), [eaaw0315]. https://doi.org/10.1126/sciadv.aaw0315

Fc receptor–like 1 intrinsically recruits c-Abl to enhance B cell activation and function. / Zhao, Xingwang; Xie, Hengyi; Zhao, Meng; Ahsan, Asma; Li, Xinxin; Wang, Fei; Yi, Junyang; Yang, Zhiyong; Wu, Chuan; Raman, Indu; Li, Quan-zhen; Kim, Tae Jin; Liu, Wanli.

In: Science Advances, Vol. 5, No. 7, eaaw0315, 17.07.2019.

Research output: Contribution to journalArticle

Zhao, X, Xie, H, Zhao, M, Ahsan, A, Li, X, Wang, F, Yi, J, Yang, Z, Wu, C, Raman, I, Li, Q, Kim, TJ & Liu, W 2019, 'Fc receptor–like 1 intrinsically recruits c-Abl to enhance B cell activation and function', Science Advances, vol. 5, no. 7, eaaw0315. https://doi.org/10.1126/sciadv.aaw0315
Zhao, Xingwang ; Xie, Hengyi ; Zhao, Meng ; Ahsan, Asma ; Li, Xinxin ; Wang, Fei ; Yi, Junyang ; Yang, Zhiyong ; Wu, Chuan ; Raman, Indu ; Li, Quan-zhen ; Kim, Tae Jin ; Liu, Wanli. / Fc receptor–like 1 intrinsically recruits c-Abl to enhance B cell activation and function. In: Science Advances. 2019 ; Vol. 5, No. 7.
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