Affinity maturation and germinal centers: how mechanism determines strategy against antigenically variable pathogens

Humans and other vertebrates are exposed to many pathogens over their lifetimes. One of the main challenges individuals’ immune systems face is the unpredictability of pathogen encounters, including those that have the ability to create new variants in order to escape recognition. The adaptive immune system has evolved to address this challenge in part by developing immunological memory. During an adaptive immune response, B cells undergo affinity maturation, a form of Darwinian evolution which produces two cell types: plasma cells, which are highly specific against past exposures, and memory B cells, which have lower affinity against previously encountered pathogens but potentially cross-react with future variants. Affinity maturation takes place in small structures known as germinal centers. In this talk, we analyze how the biophysical properties of the germinal center response enable and constrain the immune system’s ability to carry out effective strategies against pathogens, emphasizing that said strategies must account for the coupling between the dynamics of the memory repertoire and the evolution of the pathogens it protects against.