Organized mucosal associated lymphoid tissue is present in the nurse shark spiral valve 2306433

Abstract Introduction Organized mucosal associated lymphoid tissue (O-MALT), such as Peyers Patches in the mammalian gut, play a critical role in immune protection by populating the mucosa with antigen-experienced B cells. Peyer’s Patches are also reported in the gut of birds, while organized lymphocyte aggregates have been described in the gut of both reptiles and amphibians. However, bony fishes appear to lack O-MALT, instead having a diffuse network of immune cells scattered throughout the gut mucosal epithelium and lamina propria. Thus, current data suggests an increase in gut lymphoid tissue organization in a common tetrapod ancestor. Methods To test this hypothesis, we used RNAscope in situ hybridization to study immune cell organization in the spiral valve (small intestine equivalent) of the nurse shark, a member of the oldest extant vertebrate lineage to possess antibody-based adaptive immunity, the cartilaginous fishes. Results We identified O-MALT in the form of AID+  T cells and AID+ B cell follicles with strikingly morphological similarity to mammalian Peyer’s Patches in the nurse shark spiral valve. We also mapped Ig bright (plasma) cells, T cells, and MHCII+ antigen presenting cells to the spiral valve lamina propria and villi. Finally, we detected antibody in spiral valve mucus and showed it coats the gut microbiota. Conclusion Together our data indicate that the emergence of O-MALT in gut occurred much earlier than previously thought, likely in a jawed vertebrate common ancestor. Funding Source TMH was supported by NIH training grant T32AI095190. The work was partly funded by the IMET Innovations in Science Program, sponsored by the G. Unger Vetlesen Foundation, awarded to HD, and the IMET director’s fund. Topic Categories Veterinary and Comparative Immunology (VET)