Current best estimates for the average lifespans of mouse and human leukocytes: reviewing two decades of deuterium-labeling experiments

Abstract

Deuterium is a non-toxic, stable isotope that can safely be administered to humans and mice to study their cellular turnover rates in vivo. It is incorporated into newly synthesized DNA strands during cell division, without interference with the kinetics of cells, and the accumulation and loss of deuterium in the DNA of sorted (sub-)populations of leukocytes can be used to estimate their cellular production rates and lifespans. In the past two decades, this powerful technology has been used to estimate the turnover rates of various types of leukocytes. Although it is the most reliable technique currently available to study leukocyte turnover, there are remarkable differences between the cellular turnover rates estimated by some of these studies. We have recently established that part of this variation is due to (a) difficulties in estimating deuterium availability in some deuterium-labeling studies, and (b) assumptions made by the mathematical models employed to fit the data. Being aware of these two problems, we here aim to approach a consensus on the life expectancies of different types of T cells, B cells, monocytes, and neutrophils in mice and men. We address remaining outstanding problems whenever appropriate and discuss for which immune subpopulations we currently have too little information to draw firm conclusions about their turnover.

Keywords: cell proliferation; cellular lifespans; deuterium labeling; immunological memory; modeling.