Galectin-9 binds IgM-BCR to regulate B cell signaling

被引：76

作者：

Cao, Anh ^{[1
]}

Alluqmani, Nouf ^{[2
]}

Buhari, Fatima Hifza Mohammed ^{[3
]}

Wasim, Laabiah ^{[1
]}

Smith, Logan K. ^{[1
]}

Quaile, Andrew T. ^{[4
]}

Shannon, Michael ^{[5
,6
]}

Hakim, Zaki ^{[2
]}

Furmli, Hossai ^{[3
]}

Owen, Dylan M. ^{[5
,6
]}

Savchenko, Alexei ^{[4
,7
]}

Treanor, Bebhinn ^{[1
,2
,3
]}

机构：

[1] Univ Toronto, Dept Immunol, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada

[2] Univ Toronto, Dept Cell & Syst Biol, 24 Harbord St, Toronto, ON M5S 3G5, Canada

[3] Univ Toronto Scarborough, Dept Biol Sci, 1265 Mil Trail, Toronto, ON M1C 1A4, Canada

[4] Univ Toronto, Dept Chem Engn & Appl Chem, 200 Coll St, Toronto, ON M5S 3E5, Canada

[5] Kings Coll London, Dept Phys, New Hunts House,Guys Campus, London SE1 1UL, England

[6] Kings Coll London, Randall Div Cell & Mol Biophys, New Hunts House,Guys Campus, London SE1 1UL, England

[7] Univ Calgary, Hlth Res Innovat Ctr 4AA06, Cumming Sch Med, Dept Microbiol Immunol & Infect Dis, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

加拿大自然科学与工程研究理事会; 加拿大健康研究院;

关键词：

PROTEIN-TYROSINE-PHOSPHATASE; ANTIGEN RECEPTOR; T-CELLS; LIPID RAFTS; ORGANIZATION; CD22; CD45; ACTIVATION; MICRODOMAINS; EXPRESSION;

D O I：

10.1038/s41467-018-05771-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The galectin family of secreted lectins have emerged as important regulators of immune cell function; however, their role in B-cell responses is poorly understood. Here we identify IgM-BCR as a ligand for galectin-9. Furthermore, we show enhanced BCR microcluster formation and signaling in galectin-9-deficient B cells. Notably, treatment with exogenous recombinant galectin-9 nearly completely abolishes BCR signaling. We investigated the molecular mechanism for galectin-9-mediated inhibition of BCR signaling using super-resolution imaging and single-particle tracking. We show that galectin-9 merges pre-existing nanoclusters of IgM-BCR, immobilizes IgM-BCR, and relocalizes IgM-BCR together with the inhibitory molecules CD45 and CD22. In resting naive cells, we use dual-color super-resolution imaging to demonstrate that galectin-9 mediates the close association of IgM and CD22, and propose that the loss of this association provides a mechanism for enhanced activation of galectin-9-deficient B cells.

引用

页数：18

共 70 条

[1] Actin restricts FcεRI diffusion and facilitates antigen-induced receptor immobilization [J].