Inference of germinal center evolutionary dynamics via simulation-based deep learning

Abstract

B cells and the antibodies they produce are vital to health and survival, motivating research on the details of the mutational and evolutionary processes in the germinal centers (GCs) from which mature B cells arise. It is known that B cells with higher affinity for their cognate antigen (Ag) will, on average, tend to have more offspring. However, the exact form of this relationship between affinity and fecundity, which we call the "affinity-fitness response function", is not known. Here we use deep learning and simulation-based inference to learn this function from a unique experiment that replays a particular combination of GC conditions many times. All code is freely available at https://github.com/matsengrp/gcdyn, while datasets and inference results can be found at https://doi.org/10.5281/zenodo.15022130.