Numerous in vivo and in vitro studies have elucidated the basic molecular mechanisms that underlie the germinal center reaction. However, it is still not well understood how these mechanisms fit together. Mathematical models can play an important role in solving this puzzle. Unfortunately, existing studies have either used models to explain qualitative, high-level behavior without comparing simulated dynamics with quantitative experimental data, or have presented validated models that do not simulate the underlying mechanism of selection, thus neglecting important constraints on germinal center dynamics. To truly understand the mechanisms and their interactions, as well as the validity of the hypotheses incorporated in models, comprehensive models must be validated by comparison with specific experimental data.

We examine whether a specific mathematical model of germinal center dynamics, proposed by Oprea and Perelson, can reproduce experimental data from the primary response to the hapten 2-phenyl-5-oxazolone. We develop a set of formulas for estimating response-specific model parameters, as well as a discrete/stochastic implementation of the Oprea and Perelson model that enables comparison with data on individual germinal centers. Based on the available data, we conclude that while the model can reproduce the average dynamics of splenic germinal centers, the model is at best incomplete and does not reproduce the distribution of individual germinal center behaviors. Thus, better understanding and improved models are needed. In addition to suggesting a possible extension to the model, we make a number of specific predictions that can be tested by in vivo experiments to obtain further insights and validation.

A version of this technical report has been published as:

Toward quantitative simulation of germinal center dynamics: biological and modeling insights from experimental validation, J Theor Biol 2001 Aug 7;211(3):253-75.