The emergent dynamics of isotype switch.

The supplanting of the 1° IgM response by the 2° isotype-switched response is one of the best known phenomena of immune system dynamics. Given that the conditions determining which B cells will switch isotype and which ones will not are intrinsic to the entities of the immune system, it should be possible to predict the effects that the small-scale (e.g. molecular) properties have on the large scale dynamics of isotype switch. However, in practice, it is notoriously difficult to predict large scale, emergent effects from small scale conditions. Thus, it is unclear what effects (if any), mutation, IgM avidity and chronic immunization exert on isotype switch. To explore these effects, we have constructed a model of isotype switch. With this model, a modified version of the IMMSIM cellular automaton, we are able to alter small scale parameters at will and thus determine the conditions that lead to the observed large scale dynamics of isotype switch. We show that isotype switch is stabilized by high-IgM avidity, affinity/isotype-dependent cell division, and, surprisingly, mutation. We also demonstrate that chronic immunization leads, in our model, to a severe depletion of the IgM response even while the IgG response remains normal.