#2 · Systems biology

Models link non-genetic B cell state dynamics to antibody affinity maturation

The common thread is dynamical modeling of antibody affinity maturation, realized through simulation, mechanistic modeling, and learned models. Ancestra is a lineage-explicit simulator of BCR heavy-chain affinity maturation that yields sequence datasets with ground-truth lineage trees for benchmarking repertoire and lineage inference methods. A germinal center model reports that phased fragility and stability of non-genetic B cell states accelerate the genetic evolution of antibodies, treating non-genetic state variability as a factor in the rate of genetic change. A third item proposes a biologically informed training paradigm for protein language models that predicts affinity maturation trajectories. What is new is the explicit linkage of non-genetic state dynamics to the rate of genetic evolution. The other items address benchmarking and model design rather than that mechanism.