(GC-arc8) Immune-complex architecture resolves the antigen-persistence paradox in B-cell memory.

Whether persisting antigen is required for immune memory has remained unresolved despite decadesof experimental work. Genetic lineage-tracing studies demonstrate that memory B cells can persistindependently of antigen, whereas adoptive-transfer and infection models show that functional recalldecays in its absence. These findings are often treated as mutually exclusive, obscuring the possibilitythat they reflect different layers of the same system.Here we argue that immune-complex architecture provides the missing structural layer that reconcilesantigen-independent memory persistence with antigen-dependent recall. Antigen within germinal centresis retained predominantly as immune complexes whose composition, topology, and mechanical propertiesevolve over time. Early IgM- and complement-rich complexes establish stable antigen lattices that preservelong-term accessibility, while later IgG enrichment enables controlled probing and recall. Selectivedisruption of this architecture, as observed in J-chain–deficient mice, impairs memory expression withoutabolishing primary responses or affinity selection.This framework reframes immune memory as a governed, multi-layer process in which geneticpersistence, immune-complex organisation, and competition jointly determine long-term function. Bytreating antigen accessibility rather than antigen presence as the relevant variable, the antigen-persistenceparadox dissolves, and new experimentally testable predictions emerge concerning memory stability,recall kinetics, and systemic modulation of immune complexes.