DOCK2 couples with LEF-1 to regulate B cell metabolism and memory response

被引：9

作者：

Yang, Lu ^{[1
]}

Jing, Yukai ^{[2
]}

Wang, Wenjie ^{[3
]}

Ying, Wenjing ^{[3
]}

Lin, Li ^{[3
]}

Chang, Jiang ^{[1
]}

Luo, Li ^{[1
]}

Kang, Danqing ^{[1
]}

Jiang, Panpan ^{[1
]}

Liu, Ju ^{[1
]}

Chen, Qiuyue ^{[4
]}

Miller, Heather ^{[5
]}

Herrada, Andres A. ^{[6
]}

Kubo, Masato ^{[7
]}

Sun, Jinqiao ^{[3
]}

Liu, Chaohong ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pathogen Biol, Wuhan, Peoples R China

[2] Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Med Lab, Wuhan, Peoples R China

[3] Fudan Univ, Dept Clin Immunol, Childrens Hosp, Shanghai 201102, Peoples R China

[4] Yangtze Univ, Sch Med, Dept Immunol, Jingzhou, Peoples R China

[5] NIAID, Lab Intracellular Parasites, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA

[6] Univ Autonoma Chile, Fac Ciencias Salud, Inst Ciencias Biomed, Lymphat & Inflammat Res Lab, Talca, Chile

[7] RIKEN, Ctr Integrat Med Sci IMS, Lab Cytokine Regulat, Yokohama Inst, Yokohama, Kanagawa, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2020年 / 529卷 / 02期

基金：

中国国家自然科学基金;

关键词：

DOCK2; LEF-1; B cell; T-CELL; HYPOXIA; PROLIFERATION; HIF-1-ALPHA; DEFICIENCY; EXPRESSION;

D O I：

10.1016/j.bbrc.2020.05.152

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Dedicator of cytokinesis 2 (DOCK2) is essential for the B cell differentiation, BCR signaling and humoral immune response. However, the role of DOCK2 in the memory response of B cell is unknown. By using two DOCK2 deficient patients, we found that the memory B cells were decreased and the early activation of DOCK2 deficient memory B cells was abolished to the degree of naive B cells due to the decreased expression of CD19 and CD21 mechanistically. Interestingly the expression of LEF-1, a negative regulator of CD21, was increased in DOCK2 deficient B cells. This was linked to the increased expression of HIF-1 alpha and cell metabolism, which in turn affected the ER structure. Finally, the reduction of memory B cells in DOCK2 patients was due to the increased apoptosis, which might be related with the increased metabolism. (C) 2020 Published by Elsevier Inc.

引用

页码：296 / 302

页数：7

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