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BMC Immunology

, 6:23

First Online: 22 September 2005Received: 19 November 2004Accepted: 22 September 2005

Abstract

BackgroundFollicular dendritic cells FDCs play a central role in controlling B-cell response maturation, isotype switching and the maintenance of B-cell memory. These functions are based on prolonged preservation of antigen and its presentation in its native form by FDCs. However, when entrapping entire pathogens, FDCs can turn into dangerous long-term reservoirs that may preserve viruses or prions in highly infectious form.

Despite various efforts, the ontogeny of FDCs has remained elusive. They have been proposed to derive either from bone marrow stromal cells, myeloid cells or local mesenchymal precursors. Still, differentiating FDCs from their precursors in vitro may allow addressing many unsolved issues associated with the patho- biology of these important antigen-presenting cells. The aim of our study was to demonstrate that FDC-like cells can be deduced from monocytes, and to develop a protocol in order to quantitatively generate them in vitro.

ResultsEmploying highly purified human monocytes as a starter population, low concentrations of Il-4 25 U-ml and GM-CSF 3 U-ml in combination with Dexamethasone Dex 0.5 μM in serum-free medium trigger the differentiation into FDC-like cells. After transient de-novo membrane expression of alkaline phosphatase AP, such cells highly up-regulate surface expression of complement receptor I CD35. Co-expression of CD68 confirms the monocytic origin of both, AP and CD35 cells. The common leukocyte antigen CD45 is strongly down-regulated. Successive stimulation with TNF-α up-regulates adhesion molecules ICAM-1 CD54 and VCAM CD106. Importantly, both, AP as well as AP FDC-like cells, heterotypically cluster with and emperipolese B cells and exhibit the FDC characteristic ability to entrap functionally preserved antigen for prolonged times. Identical characteristics are found in monocytes which were highly expanded in vitro by higher doses of GM-CSF 25 U-ml in the absence of Dex and Il-4 before employing the above differentiation cocktail.

ConclusionIn this work we provide evidence that FDC-like cells can be derived from monocytes in vitro. Monocyte-derived FDC-like cells quantitatively produced offer a broad utility covering basic research as well as clinical application.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2172-6-23 contains supplementary material, which is available to authorized users.

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Autor: Dagmar EH Heinemann - J Hinrich Peters

Fuente: https://link.springer.com/



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