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Eur J Immunol. 2015 Jun;45(6):1621-34. doi: 10.1002/eji.201444777. Epub 2015 Apr 15.

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

Author information

1
MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing, China.
2
Collaborative Innovation Center for Infectious Diseases, Hangzhou, China.
3
Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
4
College of Engineering, Peking University, Beijing, China.
5
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
6
Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, China.
7
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China.

Abstract

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 1100 kPa). 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.

KEYWORDS:

B-cell activation; Class switch; PDMS; Proliferation; Substrate stiffness

PMID:
25756957
DOI:
10.1002/eji.201444777
[Indexed for MEDLINE]
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