Recycling probability and dynamical properties of germinal center reactions

TL;DR

This paper presents a new biologically interpretable model of germinal center reactions, emphasizing recycling of centrocytes, and predicts that high recycling rates are essential for effective immune responses.

Contribution

It introduces a simplified, parameterized model of germinal center dynamics that incorporates recycling, mutation, and selection, providing new insights into the reaction's dependence on recycling probability.

Findings

High recycling rate of centrocytes is necessary for germinal center function.

Delayed plasma and memory cell production optimizes the immune response.

Model predictions align with experimental data on germinal center dynamics.

Abstract

We introduce a new model for the dynamics of centroblasts and centrocytes in a germinal center. The model reduces the germinal center reaction to the elements considered as essential and embeds proliferation of centroblasts, point mutations of the corresponding antibody types represented in a shape space, differentiation to centrocytes, selection with respect to initial antigens, differentiation of positively selected centrocytes to plasma or memory cells and recycling of centrocytes to centroblasts. We use exclusively parameters with a direct biological interpretation such that, once determined by experimental data, the model gains predictive power. Based on the experiment of Han et al. (1995b) we predict that a high rate of recycling of centrocytes to centroblasts is necessary for the germinal center reaction to work reliably. Furthermore, we find a delayed start of the production of plasma and memory cells with respect to the start of point mutations, which turns out to be necessary for the optimization process during the germinal center reaction. The dependence of the germinal center reaction on the recycling probability is analyzed.