Markham, John F., Wellard, Cameron J., Hawkins, Edward D., Duffy, Ken R. and Hodgkin, Philip D. (2010) A minimum of two distinct heritable factors are required to explain correlation structures in proliferating lymphocytes. Journal of the Royal Society Interface, 7 (48). pp. 1049-1059. ISSN 1742-5689
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Abstract
During the adaptive immune response, lymphocyte populations undergo a characteristic
three phase process: expansion through a series of cell divisions; cessation of expansion;
and, finally, most of the accumulated lymphocytes die by apoptosis. The data used, thus
far, to inform understanding of these processes, both in vitro and in vivo, is taken from
flow cytometry experiments. One significant drawback of flow cytometry is that
individual cells cannot be tracked, so that it is not possible to investigate interdependencies
in the fate of cells within a family tree. This deficit in experimental
information has recently been overcome by Hawkins et al. (2009) who report on time
lapse microscopy experiments in which B-cells were stimulated through the TLR9
receptor. Cells stimulated in this way do not aggregate, so that data regarding family trees
can be recorded. In this article we further investigate the Hawkins et al. (2009) data. Our
conclusions are striking: in order to explain the familial correlation structure in division
times, death times and propensity to divide, a minimum of two distinct heritable factors
are necessary. As the data shows that two distinct factors are necessary, we develop a
stochastic model that has two heritable factors and demonstrate that it can reproduce the
key features of the data. This model shows that two heritable factors are sufficient. These
deductions have a clear impact upon biological understanding of the adaptive immune
response. They also necessitate changes to the fundamental premises behind the tools
developed by statisticians to draw deductions from flow cytometry data. Finally, they
affect the mathematical modelling paradigms that are used to study these systems, as
these are widely developed based on assumptions of cellular independence that are not
appropriate.
Item Type: | Article |
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Keywords: | cell lifespan; cell proliferation; cell division; mathematical model; immune response; |
Academic Unit: | Faculty of Science and Engineering > Research Institutes > Hamilton Institute |
Item ID: | 2158 |
Depositing User: | Dr Ken Duffy |
Date Deposited: | 07 Oct 2010 15:36 |
Journal or Publication Title: | Journal of the Royal Society Interface |
Publisher: | Royal Society Publishing |
Refereed: | No |
Related URLs: | |
URI: | https://mu.eprints-hosting.org/id/eprint/2158 |
Use Licence: | This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here |
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