Humoral immune responses arise when B lymphocytes respond to activation signals, enter mitosis and proliferate rapidly. Concurrent differentiation to antibody secreting and isotype switched effector cells is tightly linked to cell division, such that the degree of proliferation strongly influences the nature of the response that is mounted. Previous versions of a quantitative model of lymphocyte proliferation based on inherent variation in the time cells take to divide or die were able to accurately describe the entry of naïve, resting cells into division and subsequent population expansion. In the work described here, the model was tested and extended by investigating the proliferation cessation and population contraction phases of in vitro B cell responses. Experiments designed to assess the distribution of times to die of cells that had ceased proliferating revealed that the number of divisions achieved by individual cells is stochastically distributed in the population and varied in response to different stimuli. Both the concentration and duration of stimulation regulate the number of divisions undergone. A cell that stops dividing is described as having reached its division destiny. Further investigation revealed that cells reach a maximum division destiny even during repeated high-dose stimulation. This limit is dictated by cellular progression through divisions, and is not dependent on the survival capacity of the cells or time. Incorporation of division destiny in the quantitative model allows proliferation cessation to be described and the distribution of times to die after this point to be assessed. This extended model can describe the full course of in vitro lymphocyte proliferative responses to various different stimuli. (For complete abstract open document)
| Identifer | oai:union.ndltd.org:ADTP/245294 |
| Date | January 2008 |
| Creators | Turner, M. L. |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
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