Conditional immortalization of human B cells by CD40 ligation.

It is generally assumed that human differentiated cells have a limited life-span and proliferation capacity in vivo, and that genetic modifications are a prerequisite for their immortalization in vitro. Here we readdress this issue, studying the long-term proliferation potential of human B cells. It...

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Autores principales:	Martina Wiesner, Caroline Zentz, Christine Mayr, Rainer Wimmer, Wolfgang Hammerschmidt, Reinhard Zeidler, Andreas Moosmann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ff0fccc34347455bb1c0e05213fd2ec2
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spelling	oai:doaj.org-article:ff0fccc34347455bb1c0e05213fd2ec22021-11-25T06:13:36ZConditional immortalization of human B cells by CD40 ligation.1932-620310.1371/journal.pone.0001464https://doaj.org/article/ff0fccc34347455bb1c0e05213fd2ec22008-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18213373/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203It is generally assumed that human differentiated cells have a limited life-span and proliferation capacity in vivo, and that genetic modifications are a prerequisite for their immortalization in vitro. Here we readdress this issue, studying the long-term proliferation potential of human B cells. It was shown earlier that human B cells from peripheral blood of healthy donors can be efficiently induced to proliferate for up to ten weeks in vitro by stimulating their receptor CD40 in the presence of interleukin-4. When we applied the same stimuli under conditions of modified cell number and culture size, we were surprised to find that our treatment induced B cells to proliferate throughout an observation period of presently up to 1650 days, representing more than 370 population doublings, which suggested that these B cells were immortalized in vitro. Long-term CD40-stimulated B cell cultures could be established from most healthy adult human donors. These B cells had a constant phenotype, were free from Epstein-Barr virus, and remained dependent on CD40 ligation. They had constitutive telomerase activity and stabilized telomere length. Moreover, they were susceptible to activation by Toll-like receptor 9 ligands, and could be used to expand antigen-specific cytotoxic T cells in vitro. Our results indicate that human somatic cells can evade senescence and be conditionally immortalized by external stimulation only, without a requirement for genetic manipulation or oncoviral infection. Conditionally immortalized human B cells are a new tool for immunotherapy and studies of B cell oncogenesis, activation, and function.Martina WiesnerCaroline ZentzChristine MayrRainer WimmerWolfgang HammerschmidtReinhard ZeidlerAndreas MoosmannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 1, p e1464 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Martina Wiesner Caroline Zentz Christine Mayr Rainer Wimmer Wolfgang Hammerschmidt Reinhard Zeidler Andreas Moosmann Conditional immortalization of human B cells by CD40 ligation.
description	It is generally assumed that human differentiated cells have a limited life-span and proliferation capacity in vivo, and that genetic modifications are a prerequisite for their immortalization in vitro. Here we readdress this issue, studying the long-term proliferation potential of human B cells. It was shown earlier that human B cells from peripheral blood of healthy donors can be efficiently induced to proliferate for up to ten weeks in vitro by stimulating their receptor CD40 in the presence of interleukin-4. When we applied the same stimuli under conditions of modified cell number and culture size, we were surprised to find that our treatment induced B cells to proliferate throughout an observation period of presently up to 1650 days, representing more than 370 population doublings, which suggested that these B cells were immortalized in vitro. Long-term CD40-stimulated B cell cultures could be established from most healthy adult human donors. These B cells had a constant phenotype, were free from Epstein-Barr virus, and remained dependent on CD40 ligation. They had constitutive telomerase activity and stabilized telomere length. Moreover, they were susceptible to activation by Toll-like receptor 9 ligands, and could be used to expand antigen-specific cytotoxic T cells in vitro. Our results indicate that human somatic cells can evade senescence and be conditionally immortalized by external stimulation only, without a requirement for genetic manipulation or oncoviral infection. Conditionally immortalized human B cells are a new tool for immunotherapy and studies of B cell oncogenesis, activation, and function.
format	article
author	Martina Wiesner Caroline Zentz Christine Mayr Rainer Wimmer Wolfgang Hammerschmidt Reinhard Zeidler Andreas Moosmann
author_facet	Martina Wiesner Caroline Zentz Christine Mayr Rainer Wimmer Wolfgang Hammerschmidt Reinhard Zeidler Andreas Moosmann
author_sort	Martina Wiesner
title	Conditional immortalization of human B cells by CD40 ligation.
title_short	Conditional immortalization of human B cells by CD40 ligation.
title_full	Conditional immortalization of human B cells by CD40 ligation.
title_fullStr	Conditional immortalization of human B cells by CD40 ligation.
title_full_unstemmed	Conditional immortalization of human B cells by CD40 ligation.
title_sort	conditional immortalization of human b cells by cd40 ligation.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/ff0fccc34347455bb1c0e05213fd2ec2
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Conditional immortalization of human B cells by CD40 ligation.

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