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- Title
Profiling the origin, dynamics, and function of traction force in B cell activation.
- Authors
Wang, Junyi; Lin, Feng; Wan, Zhengpeng; Sun, Xiaolin; Lu, Yun; Huang, Jianyong; Wang, Fei; Zeng, Yingyue; Chen, Ying-Hua; Shi, Yan; Zheng, Wenjie; Li, Zhanguo; Xiong, Chunyang; Liu, Wanli
- Abstract
B lymphocytes use B cell receptors (BCRs) to recognize membrane-bound antigens to further initiate cell spreading and contraction responses during B cell activation. We combined traction force microscopy and live-cell imaging to profile the origin, dynamics, and function of traction force generation in these responses. We showed that B cell activation required the generation of 10 to 20 nN of traction force when encountering antigens presented by substrateswith stiffness values from 0.5 to 1 kPa,which mimic the rigidity of antigen-presenting cells in vivo. Perturbation experiments revealed that F-actin remodeling and myosin- and dynein-mediated contractility contributed to traction force generation and B cell activation. Moreover, membrane-proximal BCR signaling molecules (including Lyn, Syk, Btk, PLC-γ2, BLNK, and Vav3) and adaptor molecules (Grb2, Cbl, and Dok-3) linking BCR microclusters and motor proteins were also required for the sustained generation of these traction forces.We found a positive correlation between the strength of the traction force and the mean fluorescence intensity of the BCR microclusters. Furthermore, we demonstrated that isotype-switched memory B cells expressing immunoglobulin G (IgG)--BCRs generated greater traction forces than didmature naïve B cells expressing IgM-BCRs during B cell activation. Last, we observed that primary B cells from patients with rheumatoid arthritis generated greater traction forces than did B cells from healthy donors in response to antigen stimulation. Together, these data delineate the origin, dynamics, and function of traction force during B cell activation.
- Subjects
B cells; B cell receptors; MOLECULAR motor proteins; MYOSIN; IMMUNOGLOBULIN G
- Publication
Science Signaling, 2018, Vol 11, Issue 542, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.aai9192