RT Journal Article
T1 Cold-blooded vertebrates evolved organized germinal center–like structures
A1 Shibasaki, Yasuhiri
A1 Afanasyev, Sergei
A1 Fernández Montero, Álvaro
A1 Ding, Yang
A1 Watanabe, Shota
A1 Takizawa, Fumio
A1 Lamas Fernández, Jesús
A1 Fontenla Iglesias, Francisco
A1 Leiro Vidal, José Manuel
A1 Krasnov, Aleksei
A1 Boudinot, Pierre
A1 Sunyer, J. Oriol
AB Germinal centers (GCs) or analogous secondary lymphoid microstructures (SLMs) are thought to have evolved in endothermic species. However, living representatives of their ectothermic ancestors can mount potent secondary antibody responses upon infection or immunization, despite the apparent lack of SLMs in these cold-blooded vertebrates. How and where adaptive immune responses are induced in ectothermic species in the absence of GCs or analogous SLMs remain poorly understood. Here, we infected a teleost fish (trout) with the parasite Ichthyophthirius multifiliis (Ich) and identified the formation of large aggregates of highly proliferating IgM+ B cells and CD4+ T cells, contiguous to splenic melanomacrophage centers (MMCs). Most of these MMC-associated lymphoid aggregates (M-LAs) contained numerous antigen (Ag)–specific B cells. Analysis of the IgM heavy chain CDR3 repertoire of microdissected splenic M-LAs and non–M-LA areas revealed that the most frequent B cell clones induced after Ich infection were highly shared only within the M-LAs of infected animals. These M-LAs represented highly polyclonal SLMs in which Ag-specific B cell clonal expansion occurred. M-LA–associated B cells expressed high levels of activation-induced cytidine deaminase and underwent significant apoptosis, and somatic hypermutation of Igμ genes occurred prevalently in these cells. Our findings demonstrate that ectotherms evolved organized SLMs with GC-like roles. Moreover, our results also point to primordially conserved mechanisms by which M-LAs and mammalian polyclonal GCs develop and function.
PB American Association for the Advancement of Science
SN 2470-9468
YR 2023
FD 2023-11-01
LK https://hdl.handle.net/10347/45040
UL https://hdl.handle.net/10347/45040
LA eng
NO Yasuhiro Shibasaki, Sergei Afanasyev, Alvaro Fernández-Montero, Yang Ding, Shota Watanabe, Fumio Takizawa, Jesús Lamas, Francisco Fontenla-Iglesias, José Manuel Leiro, Aleksei Krasnov, Pierre Boudinot, J. Oriol Sunyer, Cold-blooded vertebrates evolved organized germinal center–like structures.Sci. Immunol.8,eadf1627(2023).DOI:10.1126/sciimmunol.adf1627
NO This work was supported by National Institutes of Health 2R01GM085207-09 (to J.O.S.), U.S. Department of Agriculture grant USDA-NIFA 2020-06446 (to J.O.S.), U.S. Department of Agriculture grant USDA-NIFA 2021-06961 (to J.O.S.), Japan Society for the Promotion of Science Overseas Research Fellowship (to Y.S.), Japan Society for the Promotion of Science KAKENHI 20 K22594 (to Y.S.), Japan Society for the Promotion of Science KAKENHI 21H02288 (to Y.S. and F.T.), Japan Society for the Promotion of Science KAKENHI 20KK0144 (to Y.S. and F.T.), and National Natural Science Foundation of China 31802337 (to Y.D.).
DS Minerva
RD 29 abr 2026