1. Academic Validation
  2. Bach2 regulates aberrant activation of B cell in systemic lupus erythematosus and can be negatively regulated by BCR-ABL/PI3K

Bach2 regulates aberrant activation of B cell in systemic lupus erythematosus and can be negatively regulated by BCR-ABL/PI3K

  • Exp Cell Res. 2018 Apr 1;365(1):138-144. doi: 10.1016/j.yexcr.2018.02.034.
Zhengwei Zhu 1 Chao Yang 1 Leilei Wen 1 Lu Liu 1 Xianbo Zuo 1 Fusheng Zhou 1 Jinping Gao 1 Xiaodong Zheng 1 Yinjuan Shi 1 Caihong Zhu 1 Bo Liang 1 Xianyong Yin 1 Wenjun Wang 1 Hui Cheng 1 Songke Shen 1 Xianfa Tang 1 Huayang Tang 1 Liangdan Sun 1 Anping Zhang 1 Sen Yang 1 Yong Cui 2 Xuejun Zhang 1 Yujun Sheng 3
Affiliations

Affiliations

  • 1 Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, Anhui 230032, China.
  • 2 Department of Dermatology, China-Japan Friendship Hospital, East Street Cherry Park, Chaoyang District, Beijing 100029, China.
  • 3 Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, Anhui 230032, China. Electronic address: [email protected].
Abstract

Objective: This study was aimed to explore the effect of Bach2 on B cells in systemic lupus erythematosus (SLE), as well as the underlying mechanisms.

Methods: Expression of Bach2, phosphorylated-Bach2 (p-Bach2), Akt, p-Akt and Bcr-Abl (p210) in B cells isolated from SLE patients and the healthy persons were assessed by Western blot. Immunofluorescence staining was performed to assess the localization of Bach2 in B cells. Enzyme-linked immunosorbent assay (ELISA) was employed to detect IgG produced by B cells. Cell counting kit-8 (CCK-8) and Annexin-V FITC/PI double staining assay were adopted to evaluate cell proliferation and Apoptosis in B cells, respectively.

Results: Compared to the healthy controls, Bach2, p-Akt and p210 were significantly decreased, while nuclear translocation of Bach2, IgG, CD40 and CD86 obviously up-regulated in B cells from SLE patients. Bach2 significantly inhibited the proliferation, promoted Apoptosis of B cells from SLE patients, whereas Bcr-Abl dramatically reversed cell changes induced by Bach2. Besides, Bcr-Abl also inhibited nuclear translocation of Bach2 in B cells from SLE patients. Further, LY294002 treatment had no effect on decreased expression of Bach2 induced by Bcr-Abl, but significantly eliminated BCR-ABL-induced phosphorylation of Bach2 and restored reduced nuclear translocation of Bach2 induced by Bcr-Abl in B cells from SLE.

Conclusions: Bach2 may play a suppressive role in B cells from SLE, and Bcr-Abl may inhibit the nuclear translocation of Bach2 via serine phosphorylation through the PI3K pathway.

Keywords

B cells; BCR-ABL; Bach2; PI3K; Systemic lupus erythematosus (SLE).

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