Pan-Jawed Vertebrate Splenic Multi-Omics Atlas Reconstructs 450-Million-Year Trajectory of Germinal Center Evolution

Germinal centers (GCs), the core microstructure of mammalian adaptive immunity, were long considered an evolutionary innovation of endotherms. Here, through systematic construction of a pan-jawed vertebrate splenic cell and spatial atlas across six evolutionary nodes, we mapped proto-germinal center (pro-GC) architectures in ectotherms and first established the evolutionary trajectory of GCs. We revealed that the core architectures of GCs, involving AICDA+ B cells, T follicular helper cells, and their interaction molecular machinery (CD40LG-CD40), were rigorously conserved across 450 million years of jawed vertebrate evolution. Notably, unlike canonical GCs in mammals with dark/light zone partitioning, pro-GCs evolved ring-polarized microdomains where MTHFD1-driven one-carbon metabolism spatially coordinates B cell proliferation, representing a specialized strategy for spatial coordination within B cell section in ectothermic vertebrates with low metabolic demands. Multimodal antigen-challenge experiments in lungfish demonstrated that the pro-GCs possess T-cell-dependent responses functionally analogous to bona fide GCs. This work traced the fundamental architecture and function of GCs to the last common ancestor of jawed vertebrates, with lineage-specific innovations emerging in endotherms and ectotherms.