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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02038

A sensitivity analysis comparison of three models for the dynamics of germinal centers

 Jose Faro1*,  Emilio Faro2, Bernardo von Haeften3 and  Rui Gardner4
  • 1Department of Biochemistry, Genetics and Immunology, University of Vigo, Spain
  • 2Departamento de Matemática Aplicada II, University of Vigo, Spain
  • 3Departamento de Física, FCEyN, National University of Mar del Plata, Argentina
  • 4Gulbenkian Institute of Science, Portugal

Germinal centers (GCs) are transient anatomical microenvironments where antibody affinity maturation and memory B cells generation takes place. In the past, models of Germinal Center (GC) dynamics have focused on understanding antibody affinity maturation rather than on the main mechanism(s) driving their rise-and-fall dynamics. Here, based on a population dynamics model core, we compare three mechanisms potentially responsible for this GC biphasic behavior dependent on follicular dendritic cell (FDC) maturation, follicular T helper (Tfh) cell maturation, and antigen depletion. Analyzing the kinetics of B and T cells, as well as its parameter sensitivities, we found that only the FDC-maturation-based model could describe realistic GC dynamics, whereas the simple Tfh-maturation and antigen-depletion mechanisms, as implemented here, could not. We also found that in all models the processes directly related to Tfh cell kinetics have the highest impact on GC dynamics. This suggests the existence of some still unknown mechanism(s) tuning GC dynamics by affecting Tfh cell response to proliferation-inducing stimuli.

Keywords: germinal center dynamics, Mathematical model analysis, Parameter sensitivity analysis, LHS method, regulation of germinal center dynamics

Received: 14 May 2019; Accepted: 12 Aug 2019.

Copyright: © 2019 Faro, Faro, von Haeften and Gardner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jose Faro, University of Vigo, Department of Biochemistry, Genetics and Immunology, Vigo, 36310, Spain,