image: 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.
Credit: ©Science Bulletin
Researchers from the Institute of Hydrobiology, Chinese Academy of Sciences have discovered previously unrecognized germinal center-like structures in the gut of common carp, providing new evidence for the early evolution of mucosal adaptive immunity.
Germinal centers are specialized sites where B cells undergo proliferation, selection and differentiation to support the production of high-affinity antibodies and long-lasting immune memory. In mammals and birds, these reactions take place within highly organized secondary lymphoid organs. Teleost fish, however, lack the classical lymphoid architecture found in mammals, raising an important question: can their mucosal tissues independently organize similar immune responses?
To address this question, the researchers examined the gut immune response of common carp following viral infection. By combining single-cell transcriptomics, fluorescence in situ hybridization and immunofluorescence, they identified previously unknown lymphoid aggregates in the intestinal tissue and termed them gut-associated germinal center-like structures, or GaGCLs.
The study showed that GaGCLs share several important features with mammalian germinal centers. B cells within these structures underwent extensive proliferation and apoptosis, while B cells expressing the chemokine receptors CXCR4 and CXCR5 displayed distinct spatial distributions. The structures also showed expression of key germinal center-associated genes, including AICDA and MKI67, indicating that the core molecular program underlying germinal center reactions is conserved in the teleost gut.
The researchers further found that viral infection promoted the accumulation of IgM-positive B cells within GaGCLs, together with increased B cell proliferation and apoptosis. Following primary infection, germinal center-like B cells gradually gave rise to memory-like B cells. After viral rechallenge, these memory-like cells were associated with increased plasma cells, IgM-positive B cells and antibody responses, suggesting that the structures contribute to the establishment and recall of mucosal B cell responses.
The study also identified T follicular helper-like cells and revealed extensive interactions between these cells and germinal center-like B cells. The conserved molecular programs and cell-cell communication networks further support the functional similarity between teleost GaGCLs and mammalian germinal centers.
The findings demonstrate that a functional germinal center-like immune response can be dynamically assembled in the teleost gut without the structural framework of conventional secondary lymphoid organs. Rather than requiring a pre-existing anatomical structure, the immune system can build a temporary organization in response to pathogen stimulation.
This discovery provides a new perspective on the evolution of mucosal adaptive immunity. It suggests that the functional components of sophisticated germinal center-like responses may have emerged in vertebrate mucosal tissues before the evolution of highly organized secondary lymphoid organs. The study therefore supports a model of "function preceding form" and points to an ancient origin of mucosal adaptive immunity in early vertebrates.
The research was conducted by the Institute of Hydrobiology, Chinese Academy of Sciences.