KINETICS OF HUMAN LYMPHOCYTE RESPONSES IN VITRO: DETERMINATION OF CLONE SIZE AND INITIAL RATE OF ENTRY INTO DNA SYNTHESIS

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Abstract
A simple stochastic model for entry of mitogen which stimulated human lymphocytes into the proliferative cycle was presented. The kinetics of lymphocyte stimulation were discussed. Responder recruitment as a process of simple exponential decay is the basis for the model. The model could be applied to the initial rapid rise in thymidine uptake after stimulation and successfully predicted behavior of colchicine inhibited mitogen responses. Application of the model allowed estimation of the following constants; size of the responding clone, rate of entry of committed cells into the initial cell cycle, duration of the lag period before uptake of thymidine increases above background and average duration of thymidine uptake in responding lymphocytes (Ts). If the experimental results of mitogen stimulation experiments are analyzed in these terms, the first 3 constants are sensitive functions of the dose of mitogen and the source of the responding lymphocytes. Low doses of mitogen seem to decrease the rate of entry of committed lymphocytes into cell cycle. This would imply that the rate-determining step in this process is not of an all or none type.