The dynamics of antibody secreting cell production: Regulation of growth and oscillations in the response to T-independent antigens

We present an interpretation and analysis of the dynamic structure of the response of antibody secreting cells to T-cell independent antigens. The observations of interest are sustained synchronous cycles in the number of such cells, and the discontinuous, “staircase” like increase in cell numbers during the first few days of the response. The main features of the model from which these results can be deduced are the existence of time delays which separate different cellular events, a particular distinction between proliferative and differentative events among the cells which will ultimately secrete antibody, and inhibition of the stimulation of the precursors of these cells by antibody already formed. In addition to describing various characteristics of cyclical antibody production, the model makes a variety of predictions related to its principal hypotheses, including the effects of antibody passively given or withdrawn on the kinetics and magnitude of the subsequent antibody response. The model also predicts, consistent with observation, the existence of an optimal dose of antigen, high and low zone unresponsiveness, and high zone tolerance. It is consistent with the phenomenon of maturation of affinity of antibody, and also predicts fluctuations in affinity. A study of the mathematical properties of the model indicates that for a wide range of parameters, the system possesses multiple steady states and limit cycle behaviour. Variations in concentrations of antigen and antibody are found to have a small influence on the frequency of oscillations, but a large influence on their amplitude.