Evidence map›Paper›PMID 18213373›Full record

ArticlePloS one2008

Conditional immortalization of human B cells by CD40 ligation.

Martina Wiesner, Caroline Zentz, Christine Mayr, Rainer Wimmer, Wolfgang Hammerschmidt, Reinhard Zeidler, Andreas Moosmann

Abstract read
In one paragraph

Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed.

  1. Trial
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  14. Genome edited B cells: a new frontier in immune cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. How Kaposi's sarcoma-associated herpesvirus stably transforms peripheral B cells towards lymphomagenesis.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  20. B Cell-Based Cancer Immunotherapy.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2019
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Martina WiesnerClinical Cooperative Group Molecular Oncology, GSF - National Research Center, Ludwig-Maximilians-Universität, Munich, Germany.
Caroline Zentz
Christine Mayr
Rainer Wimmer
Wolfgang Hammerschmidt
Reinhard Zeidler
Andreas Moosmann

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

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.

Indexed as

B-LymphocytesCD40 AntigensCell Line, TransformedFlow CytometryHumansImmunophenotypingLymphocyte ActivationTelomeraseTelomereCD40 AntigensTelomerase

Identifiers

PMID18213373
PMCPMC2180193

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.