Recirculation of germinal center B cells: a multilevel selection strategy for antibody maturation

@article{OrGuil2007RecirculationOG,
  title={Recirculation of germinal center B cells: a multilevel selection strategy for antibody maturation},
  author={Michal Or-Guil and Nicole Wittenbrink and Armin A. Weiser and Johannes Schuchhardt},
  journal={Immunological Reviews},
  year={2007},
  volume={216}
}
Summary:  Optimization of antibody affinity is a hallmark of the humoral immune response. It takes place in hundreds of transient microstructures called germinal centers (GCs). Their function and time‐dependent behavior are subjects of active investigation. According to a generally accepted notion, their individual kinetics follows the average kinetics of all GCs present in the observed lymphatic tissue. In this review, we challenge this view and point out, with the help of mathematical… 
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40 Citations
Background Citations
20
Methods Citations
1
Results Citations
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40 Citations

Broad Volume Distributions Indicate Nonsynchronized Growth and Suggest Sudden Collapses of Germinal Center B Cell Populations

This model succeeds in reproducing the empirical average kinetics of GC volumes as well as the underlying broad size distributions, indicating that individual GCs certainly do not obey the average time course of the GC volumes and that their growth is nonsynchronized.

Germinal-center organization and cellular dynamics.

How oligoclonal are germinal centers? A new method for estimating clonal diversity from immunohistological sections

BackgroundThe germinal center (GC) reaction leads to antibody affinity maturation and generation of memory B cells, but its underlying mechanisms are poorly understood. To assemble this puzzle,…

Reassessing Germinal Centre Reaction Concepts

An extended mathematical model is proposed that includes an estimation of errors created by data sampling, two new parameters that take into account possible mistakes in classification of single population GC sections, and the likely variability in the number of seeding B cells.

PopulationsSudden Collapses of Germinal Center B Cell Nonsynchronized Growth and Suggest Broad Volume Distributions Indicate

A computer-aided three-dimensional reconstructions of splenic GCs to measure size distributions at consecutive time points following immunization with a conjugate of 2-phenyl-oxazolone and chicken serum albumin reveals a broad volume distribution of GCs, indicating that individual GCs certainly do not obey the average time course of the GC volumes and that their growth is nonsynchronized.

A Major Hindrance in Antibody Affinity Maturation Investigation: We Never Succeeded in Falsifying the Hypothesis of Single-Step Selection

The single-step selection concept is proposed to be a null-hypothesis which should be attempted to be falsified, and the focus on a process of random non-directed acquisition of mutations, which minimizes the need for unverified assumptions.

Computational Model Reveals Limited Correlation between Germinal Center B-Cell Subclone Abundancy and Affinity: Implications for Repertoire Sequencing

A computational model that simulates affinity maturation in a single GC while tracking individual subclones in terms of abundancy and affinity is developed and suggests that selecting highly abundant subClones from repertoire sequencing experiments would not always lead to the high(est) affinity B cells.

Chapter 33 – Mucosal B Cell Differentiation and Regulation

Optimality of Mutation and Selection in Germinal Centers

A coarse-grained model is presented to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis of its parameter space to look for optimal values of mutation rate, selection strength, and initial antibody-antigen binding level that maximize the affinity improvement.

Models and methods for analysis of lymphocyte repertoire generation, development, selection and evolution.

References

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