Substrate stiffness regulates B-cell activation, proliferation, class switch, and T-cell-independent antibody responses in vivo

	Substrate stiffness regulates B-cell activation, proliferation, class switch, and T-cell-independent antibody responses in vivo
	Zeng, Yingyue; Yi, Junyang; Wan, Zhengpeng; Liu, Kai; Song, Ping; Chau, Alicia; Wang, Fei; Chang, Zai; Han, Weidong; Zheng, Wenjie
刊名	EUROPEAN JOURNAL OF IMMUNOLOGY
	2015
卷号	45 期号:6 页码:1621-1634
关键词	HIGH EPITOPE DENSITY ANTIGEN RECEPTOR IMMUNOLOGICAL SYNAPSES MECHANICAL-PROPERTIES PROTEIN MOLECULE ADHESION GROWTH DISCRIMINATION LYMPHOCYTES ELASTICITY
通讯作者	Liu, WL (reprint author), Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
产权排序	5
合作状况	国内
英文摘要	B cells use B-cell receptors (BCRs) to sense antigens that are usually presented on substrates with different stiffness. However, it is not known how substrate stiffness affects B-cell proliferation, class switch, and in vivo antibody responses. We addressed these questions using polydimethylsiloxane (PDMS) substrates with different stiffness (20 or 1100kPa). Live cell imaging experiments suggested that antigens on stiffer substrates more efficiently trigger the synaptic accumulation of BCR and phospho-Syk molecules compared with antigens on softer substrates. In vitro expansion of mouse primary B cells shows different preferences for substrate stiffness when stimulated by different expansion stimuli. LPS equally drives B-cell proliferation on stiffer or softer substrates. Anti-CD40 antibodies enhance B-cell proliferation on stiffer substrates, while antigens enhance B-cell proliferation on softer substrates through a mechanism involving the enhanced phosphorylation of PI3K, Akt, and FoxO1. In vitro class switch differentiation of B cells prefers softer substrates. Lastly, NP67-Ficoll on softer substrates accounted for an enhanced antibody response in vivo. Thus, substrate stiffness regulates B-cell activation, proliferation, class switch, and T cell independent antibody responses in vivo, suggesting its broad application in manipulating the fate of B cells in vitro and in vivo.
学科主题	Immunology
类目[WOS]	Immunology
收录类别	SCI
语种	英语
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/27581]
专题	成都生物研究所_天然产物研究
推荐引用方式 GB/T 7714	Zeng, Yingyue,Yi, Junyang,Wan, Zhengpeng,et al. Substrate stiffness regulates B-cell activation, proliferation, class switch, and T-cell-independent antibody responses in vivo[J]. EUROPEAN JOURNAL OF IMMUNOLOGY,2015,45(6):1621-1634.
APA	Zeng, Yingyue.,Yi, Junyang.,Wan, Zhengpeng.,Liu, Kai.,Song, Ping.,...&Liu, Wanli.(2015).Substrate stiffness regulates B-cell activation, proliferation, class switch, and T-cell-independent antibody responses in vivo.EUROPEAN JOURNAL OF IMMUNOLOGY,45(6),1621-1634.
MLA	Zeng, Yingyue,et al."Substrate stiffness regulates B-cell activation, proliferation, class switch, and T-cell-independent antibody responses in vivo".EUROPEAN JOURNAL OF IMMUNOLOGY 45.6(2015):1621-1634.