biostudies-literatureUnknownHasan ANCI NIH HHSNIGMS NIH HHSThe thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self, antigens. B cells also reside and develop in the thymus, although their functions are less clear. During 'thymic involution,' a process of lymphoid atrophy and adipose replacement linked to sexual maturation, thymocytes decline. However, thymic B cells decrease far less than T cells, such that B cells comprise ~1% of human neonatal thymocytes, but up to ~10% in adults. All jawed vertebrates possess a thymus, and we and others have shown zebrafish (<i>Danio rerio</i>) also have thymic B cells. Here, we investigated the precise identities of zebrafish thymic T and B cells and how they change with involution. We assessed the timing and specific details of zebrafish thymic involution using multiple lymphocyte-specific, fluorophore-labeled transgenic lines, quantifying the changes in thymic T- and B-lymphocytes pre- vs. post-involution. Our results prove that, as in humans, zebrafish thymic B cells increase relative to T cells post-involution. We also performed RNA sequencing (RNA-seq) on <i>D. rerio</i> thymic and marrow lymphocytes of four novel double-transgenic lines, identifying distinct populations of immature T and B cells. Collectively, this is the first comprehensive analysis of zebrafish thymic involution, demonstrating its similarity to human involution, and establishing the highly genetically-manipulatable zebrafish model as a template for involution studies.bioRxiv : the preprint server for biology2023.07.25.550519https://www.ebi.ac.uk/biostudies/studies/S-EPMC10402004biostudies-literatureDynamic Changes in Lymphocyte Populations Establish Zebrafish as a Thymic Involution Model.PMC10402004P30 CA225520P20 GM103639Hasan APark GFrazer JKWood BMalone-Perez MMacias JJFoster CAfalseDynamic Changes in Lymphocyte Populations Establish Zebrafish as a Thymic Involution Model.The thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self, antigens. B cells also reside and develop in the thymus, although their functions are less clear. During 'thymic involution,' a process of lymphoid atrophy and adipose replacement linked to sexual maturation, thymocytes decline. However, thymic B cells decrease far less than T cells, such that B cells comprise ~1% of human neonatal thymocytes, but up to ~10% in adults. All jawed vertebrates possess a thymus, and we and others have shown zebrafish (<i>Danio rerio</i>) also have thymic B cells. Here, we investigated the precise identities of zebrafish thymic T and B cells and how they change with involution. We assessed the timing and specific details of zebrafish thymic involution using multiple lymphocyte-specific, fluorophore-labeled transgenic lines, quantifying the changes in thymic T- and B-lymphocytes pre- vs. post-involution. Our results prove that, as in humans, zebrafish thymic B cells increase relative to T cells post-involution. We also performed RNA sequencing (RNA-seq) on <i>D. rerio</i> thymic and marrow lymphocytes of four novel double-transgenic lines, identifying distinct populations of immature T and B cells. Collectively, this is the first comprehensive analysis of zebrafish thymic involution, demonstrating its similarity to human involution, and establishing the highly genetically-manipulatable zebrafish model as a template for involution studies.2023-01-01T00:00:00Z2023 Jul2026-04-08T13:35:35.973Z2026-04-08T03:13:36.239ZS-EPMC104020043754678810.1101/2023.07.25.550519