Interpreting CFSE Obtained Division Histories of B Cells in Vitro with Smith–Martin and Cyton Type Models
- 21 April 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Bulletin of Mathematical Biology
- Vol. 71 (7), 1649-1670
- https://doi.org/10.1007/s11538-009-9418-6
Abstract
The fluorescent dye carboxyfluorescin diacetate succinimidyl ester (CFSE) classifies proliferating cell populations into groups according to the number of divisions each cell has undergone (i.e., its division class). The pulse labeling of cells with radioactive thymidine provides a means to determine the distribution of times of entry into the first cell division. We derive in analytic form the number of cells in each division class as a function of time using the cyton approach that utilizes independent stochastic distributions for the time to divide and the time to die. We confirm that our analytic form for the number of cells in each division class is consistent with the numerical solution of a set of delay differential equations representing the generalized Smith–Martin model with cell death rates depending on the division class. Choosing the distribution of time to the first division to fit thymidine labeling data for B cells stimulated in vitro with lipopolysaccharide (LPS) and either with or without interleukin-4 (IL-4), we fit CFSE data to determine the dependence of B cell kinetic parameters on the presence of IL-4. We find when IL-4 is present, a greater proportion of cells are recruited into division with a longer average time to first division. The most profound effect of the presence of IL-4 was decreased death rates for smaller division classes, which supports a role of IL-4 in the protection of B cells from apoptosis.Keywords
This publication has 36 references indexed in Scilit:
- A model of immune regulation as a consequence of randomized lymphocyte division and death timesProceedings of the National Academy of Sciences of the United States of America, 2007
- Quantifying lymphocyte kinetics in vivo using carboxyfluorescein diacetate succinimidyl esterProceedings Of The Royal Society B-Biological Sciences, 2006
- Estimating division and death rates from CFSE dataJournal of Computational and Applied Mathematics, 2005
- A general mathematical framework to model generation structure in a population of asynchronously dividing cellsJournal of Theoretical Biology, 2004
- The Bcl-2 family: roles in cell survival and oncogenesisOncogene, 2003
- Carboxyfluorescein diacetate succinimidyl ester and the virgin lymphocyte: A marriage made in heavenImmunology & Cell Biology, 1999
- Analysis of growth kinetics by division trackingImmunology & Cell Biology, 1999
- Interleukin-4 enhances anti-IgM stimulation of B cells by improving cell viability and by increasing the sensitivity of b cells to the anti-IgM signalCellular Immunology, 1991
- Human B cell clones can be induced to proliferate and to switch to IgE and IgG4 synthesis by interleukin 4 and a signal provided by activated CD4+ T cell clones.The Journal of Experimental Medicine, 1991
- Bootstrap Methods for Standard Errors, Confidence Intervals, and Other Measures of Statistical AccuracyStatistical Science, 1986