How to Simulate a Germinal Center

Germinal centers host a mini-evolutionary environment where B cells can mutate their receptor and be selected depending on its affinity to target antigens in a process called affinity maturation. Starting from founder cells with a weak B cell receptor affinity, germinal centers release output cells as antibody-secreting cells or memory cells with a very high affinity, a property which is essential for pathogen clearance and immune memory. Therapeutic interventions on the germinal centers are tantalizing approaches to improve vaccines or to support rejection of chronic pathogens such as HIV. However, the complexity of the selection processes makes it very hard to make reliable predictions. Here, we present in detail how to build an agent-based model (hyphasma), accounting for the dynamics of the germinal center. It encompasses the core quantitative traits of affinity maturation, and allowed to make reliable predictions in previous studies.