Schematic representation of the spatial organization and cellular architecture of gut-associated germinal center-like structures (GaGCLs) in teleost fish (IMAGE)
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The origin of bona fide GaGCL in vertebrates can be traced back approximately 200 million years ago in birds, marking a critical evolutionary milestone in the development of the mucosal adaptive immune system. This study demonstrates GC-like functional structures in the teleost fish gut, shedding light on the evolutionary origins of GCs. They established a viral infection model using SVCV oral gavage, which triggered pathological changes and strong immune responses in the gut. scRNA-seq revealed key ligand-receptor interactions between T and B cells driving GC reactions, including ALCAM-CD6, TNFSF14-TNFRSF14, TGFB1-TGFBR3, and TNFSF14-LTBR. Notably, GaGCL structures were identified within the gut LP, characterized by spatial gradients of cxcr4+ and cxcr5+ expression, elevated expression of aicda+ and mki67+ transcripts, and co-localization of SVCV-specific IgM+ B cells. Additionally, significant B cell proliferation alongside apoptosis was uniquely observed within these GaGCLs in infected fish. These results suggest that gut cell types and functional characteristics are similar between teleost and mammals. This establishes the evolutionary principle of “function preceding form” and traces the origin of sophisticated mucosal adaptive immunity back to early teleost.
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