Abstract
Intravital imaging of antibody optimization in germinal center (GC) reactions has set a new dimension in the understanding of the humoral immune response during the last decade. The inclusion of spatio-temporal cellular dynamics in the research on GCs required analysis using the agent-based mathematical models. In this study, we integrate the available intravital imaging data from various research groups and incorporate these into a quantitative mathematical model of GC reactions and antibody affinity maturation. Interestingly, the integration of data concerning the spatial organization of GCs and B cell motility allows to draw conclusions on the strength of the selection pressure and the control of B cell division by T follicular helper cells.
Highlights
Germinal centers (GCs) are specialized environments normally located in lymphoid tissues giving rise to high-affinity antibodies [1, 2]
GCs exhibit a specific spatial organization in dark zone (DZ) and light zone (LZ) [11], which is due to highly motile B and T cells, respectively
While T cells are mostly found in the LZ [12], B cells are sorted according to the differentiation state: dividing and mutating B cells are concentrated in the DZ while B cells in the state of competitive selection are in the LZ
Summary
Germinal centers (GCs) are specialized environments normally located in lymphoid tissues giving rise to high-affinity antibodies [1, 2]. Soluble high-affinity antibodies that are derived from the GC product, namely the plasma cells, feed back onto the GC reaction itself by covering the antigen presented on the FDC network [26] These recent developments led to an extension of the mathematical models to include antibody feedback, DND [27], and continuous influx of founder clones into GCs [25]. In view of the tight connection between the spatial dynamics of GC B cells and B cell selection, we asked whether it would be possible to derive the strength of competition and the number of induced B cell divisions after recycling from the integrated two-photon data on B cell motility in GCs. The significant changes in the model represent the inclusion of a large body of new research. We show that DND is required to reproduce experimental results and specify the related model parameters for the first time
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