Dynamics of one-pass germinal center models: implications for affinity maturation

Area of Science:

• Immunology
• Computational Biology
• Molecular Biology

Background:

• Antibody affinity maturation increases antibody effectiveness over time during immune responses.
• This process involves somatic hypermutation of immunoglobulin genes and selection of high-affinity B cell variants within germinal centers.
• Existing models often assume a multi-step mutation and selection process within germinal centers.

Purpose of the Study:

• To investigate whether a single-pass mechanism of mutation and selection can explain the observed efficiency of affinity maturation.
• To analyze one-pass models of the germinal center reaction with decaying antigen and mutation at transcription or replication.

Main Methods:

• Analysis of one-pass mathematical models of the germinal center reaction.
• Modeling antigen decay and mutation occurrence during B cell gene transcription or replication.
• Evaluating model output against experimental data on affinity maturation efficiency.

Main Results:

• The proportion of high-affinity cells in the output of a germinal center varies logarithmically with selection probability in one-pass models.
• For biologically realistic parameters, the efficiency of single-pass mutation-selection models is insufficient to explain experimental data.
• The study highlights potential limitations of models assuming no post-selection amplification.

Conclusions:

• A single-pass mutation and selection mechanism is unlikely to account for the high efficiency of antibody affinity maturation.
• The findings suggest that multi-step processes or alternative mechanisms may be necessary to explain experimental observations.
• The analysis provides insights into selection dynamics in populations subjected to decaying selective forces.