A model of immune regulation as a consequence of randomized lymphocyte division and death times
- Author(s)
- Hawkins, ED; Turner, ML; Dowling, MR; van Gend, C; Hodgkin, PD;
- Details
- Publication Year 2007-03-20,Volume 104,Issue #12,Page 5032-5037
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- The magnitude of an adaptive immune response is controlled by the interplay of lymphocyte quiescence, proliferation, and apoptosis. How lymphocytes integrate receptor-mediated signals influencing these cell fates is a fundamental question for understanding this complex system. We examined how lymphocytes interleave times to divide and die to develop a mathematical model of lymphocyte growth regulation. This model provides a powerful method for fitting and analyzing fluorescent division tracking data and reveals how summing receptor-mediated kinetic changes can modify the immune response progressively from rapid tolerance induction to strong immunity. An important consequence of our results is that intrinsic variability in otherwise identical cells, usually dismissed as noise, may have evolved to be an essential feature of immune regulation.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- STIMULATORY FACTOR-I; T-CELL RESPONSES; B-CELLS; TRANSITION-PROBABILITY; BYSTANDER ACTIVATION; GENERATION TIMES; GENE-EXPRESSION; VIRAL-INFECTION; CFSE DATA; DIFFERENTIATION
- Publisher's Version
- https://doi.org/10.1073/pnas.0700026104
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2007-03-20 12:00:00