The lifecycle of a B cell

B cells are the central actors in the adaptive system and encode highly diverse and mutable pathogen-engaging receptors. They can counter a multitude of pathogens by directly neutralizing invaders or by storing memory to respond to reinfections efficiently. Upon infection, activated B cells seed germinal centers (GCs) where they hypermutate and are selected for enhanced affinity to pathogens. On longer timescales, memory B cells from previous GC reactions can seed new GCs during reinfection and mutate further; however, the extent of their role in response to reinfections is unclear. Because B cells evolve only in GCs, standard dynamical models with continuous accumulation of mutations fail to describe this interrupted evolution. We introduce a stochastic telegraph process to model the B-cell lifecycle by capturing the entry and exit of B cells from GCs and constraining the accumulation of mutations to the GC residents only. We use this model to reconstruct time-resolved evolutionary histories of B cells from a longitudinal dataset of immune repertoires from individuals with HIV and obtain posteriors of the rates across repertoires and patients. Our results elucidate the lifecycle of B cells and clarify the role of memory B cells in secondary responses on a repertoire-wide scale.