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

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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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ASJC Scopus subject areas

  • Physics and Astronomy (miscellaneous)
  • General

Cite this

Zhao, X., Xie, H., Zhao, M., Ahsan, A., Li, X., Wang, F., Yi, J., Yang, Z., Wu, C., Raman, I., Li, Q. Z., Kim, T. J., & 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