RT Journal Article T1 Dysregulation of B cell activity during proliferative kidney disease in rainbow trout A1 Abós Gracia, Beatriz A1 Estensoro, Itziar A1 Perdiguero Jiménez, Pedro A1 Faber, Marc A1 Hu, Yehfang A1 Díaz Rosales, Patricia A1 Granja, Aitor A1 Secombes, Christopher A1 Holland, Jason A1 Tafalla, Carolina AB Proliferative kidney disease (PKD) is a widespread disease caused by the endoparasite Tetracapsuloides bryosalmonae (Myxozoa: Malacosporea). Clinical disease, provoked by the proliferation of extrasporogonic parasite stages, is characterized by a chronic kidney pathology with underlying transcriptional changes indicative of altered B cell responses and dysregulated T-helper cell-like activities. Despite the relevance of PKD to European and North American salmonid aquaculture, no studies, to date, have focused on further characterizing the B cell response during the course of this disease. Thus, in this work, we have studied the behavior of diverse B cell populations in rainbow trout (Oncorhynchus mykiss) naturally infected with T. bryosalmonae at different stages of preclinical and clinical disease. Our results show a clear upregulation of all trout immunoglobulins (Igs) (IgM, IgD, and IgT) demonstrated by immunohistochemistry and Western blot analysis, suggesting the alteration of diverse B cell populations that coexist in the infected kidney. Substantial changes in IgM, IgD, and IgT repertoires were also identified throughout the course of the disease further pointing to the involvement of the three Igs in PKD through what appear to be independently regulated mechanisms. Thus, our results provide strong evidence of the involvement of IgD in the humoral response to a specific pathogen for the first time in teleosts. Nevertheless, it was IgT, a fish-specific Ig isotype thought to be specialized in mucosal immunity, which seemed to play a prevailing role in the kidney response to T. bryosalmonae. We found that IgT was the main Ig coating extrasporogonic parasite stages, IgT+ B cells were the main B cell subset that proliferated in the kidney with increasing kidney pathology, and IgT was the Ig for which more significant changes in repertoire were detected. Hence, although our results demonstrate a profound dysregulation of different B cell subsets during PKD, they point to a major involvement of IgT in the immune response to the parasite. These results provide further insights into the pathology of PKD that may facilitate the future development of control strategies PB Frontiers YR 2018 FD 2018 LK https://hdl.handle.net/20.500.14352/96714 UL https://hdl.handle.net/20.500.14352/96714 LA eng NO Abos, Beatriz, et al. «Dysregulation of B Cell Activity During Proliferative Kidney Disease in Rainbow Trout». Frontiers in Immunology, vol. 9, mayo de 2018, p. 1203. https://doi.org/10.3389/fimmu.2018.01203. NO FundingThis work was supported by the European Research Council (ERC Consolidator Grant 2016 725061 TEMUBLYM) and the European Commission under the H2020 Programme (Grant H2020-634429 ParaFishControl). IE was recipient of APOSTD/2016/037 grant by the “Generalitat Valenciana” and YH was recipient of a PhD Studentship from the Ministry of Education, Republic of China (Taiwan). JWH was supported by BBSRC grant BB/K009125/1 and SNSF grant CRSII3_147649-1. PDR was funded by grant T1-BIO-1672 from the “Comunidad de Madrid”. NO European Commission NO Generalitat Valenciana NO Ministry of Education (China) NO Comunidad de Madrid DS Docta Complutense RD 9 abr 2025