Transmembrane domain dependent inhibitory function of FcγRIIB

doi:10.1007/s13238-018-0509-8

Protein Cell

2018, Vol. 9

Issue (12) : 1004-1012 https://doi.org/10.1007/s13238-018-0509-8

REVIEW

Transmembrane domain dependent inhibitory function of FcγRIIB

Junyi Wang¹, Zongyu Li¹, Liling Xu²(

), Hengwen Yang³(

), Wanli Liu¹(

)

¹. MOE Key Laboratory of Protein Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences, Tsinghua University, Beijing 100084, China
². Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard University, 400 Technology Square, Cambridge, MA 02139, USA
³. The First Affiliate Hospital, Biomedical Translational Research Institute, Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Jinan University, Guangzhou 510632, China

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Abstract

FcγRIIB, the only inhibitory IgG Fc receptor, functions to suppress the hyper-activation of immune cells. Numerous studies have illustrated its inhibitory function through the ITIM motif in the cytoplasmic tail of FcγRIIB. However, later studies revealed that in addition to the ITIM, the transmembrane (TM) domain of FcγRIIB is also indispensable for its inhibitory function. Indeed, recent epidemiological studies revealed that a non-synonymous single nucleotide polymorphism (rs1050501) within the TM domain of FcγRIIB, responsible for the I232T substitution, is associated with the susceptibility to systemic lupus erythematosus (SLE). In this review, we will summarize these epidemiological and functional studies of FcγRIIB-I232T in the past few years, and will further discuss the mechanisms accounting for the functional loss of FcγRIIB-I232T. Our review will help the reader gain a deeper understanding of the importance of the TM domain in mediating the inhibitory function of FcγRIIB and may provide insights to a new therapeutic target for the associated diseases.

Keywords B cell FcγRIIB transmembrane domain systemic lupus erythematosus autoimmune disease

Corresponding Author(s): Liling Xu,Hengwen Yang,Wanli Liu

Issue Date: 19 December 2018

Cite this article:

Junyi Wang,Zongyu Li,Liling Xu, et al. Transmembrane domain dependent inhibitory function of FcγRIIB[J]. Protein Cell, 2018, 9(12): 1004-1012.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-018-0509-8
https://academic.hep.com.cn/pac/EN/Y2018/V9/I12/1004

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