(GC_arc12)Governed diversification in germinal centres: from somatic hypermutation to adaptive computation

Germinal centres (GCs) enable the immune system to explore an extraordi-
narily large mutational space while reliably producing functional, non-pathogenic
outcomes. Classical descriptions frame this process as stochastic mutation followed
by selection. However, accumulating evidence suggests that GC dynamics are bet-
ter understood as a governed system, in which diversification is constrained by
regulatory architecture operating across molecular, cellular, and tissue scales.
In this Review, we synthesise advances in somatic hypermutation (SHM) bi-
ology, B–T cell signalling, enhancer architecture, and systems-level modelling to
argue that GC evolution is neither blind nor purely competitive. Instead, it resem-
bles a capacity-limited adaptive process in which mutational exploration is biased,
pruned, and stabilised through feedback mechanisms that preserve learnability. We
discuss how such governance reconciles SHM with neutral theory, prevents clonal
collapse, and enables repertoire shifts over time. Finally, we outline how this per-
spective informs cancer biology, immune memory, and broader principles of biolog-
ical computation.