Subcellular topography modulates actin dynamics and signaling in B-cells

被引:22
作者
Ketchum, Christina M. [1 ]
Sun, Xiaoyu [2 ]
Suberi, Alexandra [2 ]
Fourkas, John T. [2 ,3 ,4 ,5 ]
Song, Wenxia [6 ]
Upadhyaya, Arpita [1 ,3 ,7 ]
机构
[1] Univ Maryland, Biophys Program, College Pk, MD 20742 USA
[2] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA
[3] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA
[4] Univ Maryland, Ctr Nanophys & Adv Mat, College Pk, MD 20742 USA
[5] Univ Maryland, Maryland NanoCtr, College Pk, MD 20742 USA
[6] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA
[7] Univ Maryland, Dept Phys, College Pk, MD 20742 USA
基金
美国国家卫生研究院;
关键词
FOLLICULAR DENDRITIC CELLS; BRUTONS TYROSINE KINASE; T-CELLS; ANTIGEN RECEPTOR; CALCIUM OSCILLATIONS; SYNAPSE FORMATION; CORTICAL ACTIN; LYMPH-NODES; IN-VIVO; ACTIVATION;
D O I
10.1091/mbc.E17-06-0422
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
B-cell signaling activation is most effectively triggered by the binding of B-cell receptors (BCRs) to membrane-bound antigens. In vivo, B-cells encounter antigen on antigen-presenting cells (APC), which possess complex surfaces with convoluted topographies, a fluid membrane and deformable cell bodies. However, whether and how the physical properties of antigen presentation affect B-cell activation is not well understood. Here we use nanotopographic surfaces that allow systematic variation of geometric parameters to show that surface features on a subcellular scale influence B-cell signaling and actin dynamics. Parallel nanoridges with spacings of 3 microns or greater induce actin intensity oscillations on the ventral cell surface. Nanotopography-induced actin dynamics requires BCR signaling, actin polymerization, and myosin contractility. The topography of the stimulatory surface also modulates the distribution of BCR clusters in activated B-cells. Finally, B-cells stimulated on nanopatterned surfaces exhibit intracellular calcium oscillations with frequencies that depend on topography. Our results point to the importance of physical aspects of ligand presentation, in particular, nanotopography for B-cell activation and antigen gathering.
引用
收藏
页码:1732 / 1742
页数:11
相关论文
共 65 条
[1]   Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation [J].
Arana, Eloisa ;
Vehlow, Anne ;
Harwood, Naomi E. ;
Vigorito, Elena ;
Henderson, Robert ;
Turner, Martin ;
Tybulewicz, Victor L. J. ;
Batista, Facundo D. .
IMMUNITY, 2008, 28 (01) :88-99
[2]   Highways, byways and breadcrumbs: directing lymphocyte traffic in the lymph node [J].
Bajenoff, Marc ;
Egen, Jackson G. ;
Qi, Hai ;
Huan, Alex Y. C. ;
Castellino, Flora ;
Germain, Ronald N. .
TRENDS IN IMMUNOLOGY, 2007, 28 (08) :346-352
[3]   Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes [J].
Bajenoff, Marc ;
Egen, Jackson G. ;
Koo, Lily Y. ;
Laugier, Jean Pierre ;
Brau, Frederic ;
Glaichenhaus, Nicolas ;
Germain, Ronald N. .
IMMUNITY, 2006, 25 (06) :989-1001
[4]   B-cell follicle development remodels the conduit system and allows soluble antigen delivery to follicular dendritic cells [J].
Bajenoff, Marc ;
Germain, Ronald N. .
BLOOD, 2009, 114 (24) :4989-4997
[5]   Visualizing a role for the actin cytoskeleton in the regulation of B-cell activation [J].
Batista, Facundo D. ;
Treanor, Bebhinn ;
Harwood, Naomi E. .
IMMUNOLOGICAL REVIEWS, 2010, 237 :191-204
[6]   B cells acquire antigen from target cells after synapse formation [J].
Batista, FD ;
Iber, D ;
Neuberger, MS .
NATURE, 2001, 411 (6836) :489-494
[7]   Signal transduction by the B-cell antigen receptor [J].
DeFranco, AL ;
Richards, JD ;
Blum, JH ;
Stevens, TL ;
Law, DA ;
Chan, VWF ;
Datta, SK ;
Foy, SP ;
Hourihane, SL ;
Gold, MR ;
Matsuuchi, L .
RECEPTOR ACTIVATION BY ANTIGENS, CYTOKINES, HORMONES, AND GROWTH FACTORS, 1995, 766 :195-201
[8]   CD19 is essential for B cell activation by promoting B cell receptor-antigen microcluster formation in response to membrane-bound ligand [J].
Depoil, David ;
Fleire, Sebastian ;
Treanor, Bebhinn L. ;
Weber, Michele ;
Harwood, Naomi E. ;
Marchbank, Kevin L. ;
Tybulewicz, Victor L. J. ;
Batista, Facundo D. .
NATURE IMMUNOLOGY, 2008, 9 (01) :63-72
[9]   Calcium oscillations increase the efficiency and specificity of gene expression [J].
Dolmetsch, RE ;
Xu, KL ;
Lewis, RS .
NATURE, 1998, 392 (6679) :933-936
[10]   Cellular Contact Guidance through Dynamic Sensing of Nanotopography [J].
Driscoll, Meghan K. ;
Sun, Xiaoyu ;
Guven, Can ;
Fourkas, John T. ;
Losert, Wolfgang .
ACS NANO, 2014, 8 (04) :3546-3555