Toward quantitative simulation of germinal center dynamics. I. Biologicaland modeling insights from experimental validation

Abstract:

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.