Commitment and proliferation kinetics of human lymphocytes stimulated in vitro: Effects of α‐MM addition and suboptimal dose on concanavalin a response

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Abstract
We have examined the effect of alpha‐methylmannoside (α‐MM) addition to concanavalin A (con A)‐stimulated peripheral human lymphocytes. With a previously established kinetic model, we have, from the time course of proliferation, extracted the responding clone size, rate of entry of this clone into S phase, and the length of the lag period. We have studied the effect of con A dose and time of addition of α‐MM to optimally stimulated cells on these kinetic parameters. We show that neither a low dose of con A nor an early addition of ‐‐MM to optimally stimulated cells results in a change in the responding clone size. That is, all of the potentially responsive cells appear to become “committed” to enter the cell cycle regardless of the presence of α‐MM early in the culture or in the presence of suboptimal stimulation. However, the rate at which these committed cells enter the first S phase is a function of the dose of con A and time of addition of α‐MM and varies over a wide range. It is the variation in this parameter that accounts for virtually all of the diminished response previously interpreted as a time‐dependent irreversible commitment of mitogen‐stimulated cells. The previous work using only fixed time points for measuring thymidine uptake and the concept of commitment must be reevaluated in light of the kinetic evidence presented.