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Cell Mol Life Sci. 2016 Dec;73(23):4531-4545. Epub 2016 Apr 28.

The growth determinants and transport properties of tunneling nanotube networks between B lymphocytes.

Author information

1
Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
2
Department of Biophysics, Medical Faculty, University of Pécs, Pecs, Hungary.
3
MTA-PTE Nuclear-Mitochondrial Interactions Research Group, Pecs, Hungary.
4
Department of Biochemistry, Eötvös Loránd University, Budapest, Hungary.
5
Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.
6
Environmental Chemistry Research Group, Research Centre for Natural Sciences, Budapest, Hungary.
7
MTA-SE Molecular Biophysics Research Group, Budapest, Hungary.
8
Department of Immunology, Eötvös Loránd University, Budapest, Hungary. janos.matko@ttk.elte.hu.

Abstract

Tunneling nanotubes (TNTs) are long intercellular connecting structures providing a special transport route between two neighboring cells. To date TNTs have been reported in different cell types including immune cells such as T-, NK, dendritic cells, or macrophages. Here we report that mature, but not immature, B cells spontaneously form extensive TNT networks under conditions resembling the physiological environment. Live-cell fluorescence, structured illumination, and atomic force microscopic imaging provide new insights into the structure and dynamics of B cell TNTs. Importantly, the selective interaction of cell surface integrins with fibronectin or laminin extracellular matrix proteins proved to be essential for initiating TNT growth in B cells. These TNTs display diversity in length and thickness and contain not only F-actin, but their majority also contain microtubules, which were found, however, not essential for TNT formation. Furthermore, we demonstrate that Ca2+-dependent cortical actin dynamics exert a fundamental control over TNT growth-retraction equilibrium, suggesting that actin filaments form the TNT skeleton. Non-muscle myosin 2 motor activity was shown to provide a negative control limiting the uncontrolled outgrowth of membranous protrusions. Moreover, we also show that spontaneous growth of TNTs is either reduced or increased by B cell receptor- or LPS-mediated activation signals, respectively, thus supporting the critical role of cytoplasmic Ca2+ in regulation of TNT formation. Finally, we observed transport of various GM1/GM3+ vesicles, lysosomes, and mitochondria inside TNTs, as well as intercellular exchange of MHC-II and B7-2 (CD86) molecules which may represent novel pathways of intercellular communication and immunoregulation.

KEYWORDS:

Fluorescence imaging; Intercellular matter transport; Membrane nanotubes; Membrane protrusion; Superresolution microscopy; Trogocytosis

PMID:
27125884
DOI:
10.1007/s00018-016-2233-y
[Indexed for MEDLINE]

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