Theory 12/Life, Medicine & Mind /Immunology
Affinity Follows Dwell Time
Maturation is attributed to antigen availability. The number of rounds may matter more.
Antibody affinity maturation is set by the dwell time of B cells in the germinal centre rather than by antigen dose, so more dwell cycles per unit time, not more antigen, produce higher affinity.
01The evidence
Affinity maturation continues for weeks after antigen is cleared, which is hard to reconcile with dose-limited selection.
02The tension
Dose models predict maturation should slow when antigen falls. It often continues.
03The mechanism
Each germinal centre cycle offers a chance for mutation and selection. The total improvement is the product of cycles, so dwell time and recycling rate set affinity.
That makes the number of cycles the determinant, and predicts that increasing cycling rate at constant antigen should raise affinity.
04What this is not
Dose models make antigen the limiter. This makes cycles the limiter.
05Predictions
- P1Affinity should track cycle number.
- P2Maturation should continue after antigen clearance.
- P3Cycling rate should predict affinity.
06Refutation
Affinity tracking antigen dose at controlled cycling would restore the dose model.
07What it changes
It would change vaccine adjuvant strategy.