Dynamic Changes in Lymphocyte Populations Establish Zebrafish as a Thymic Involution Model

J Immunol. 2024 Jun 1;212(11):1733-1743. doi: 10.4049/jimmunol.2300495.


The thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self, Ags. 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 (Danio rerio) also have thymic B cells. In this article, 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- versus postinvolution. Our results prove that, as in humans, zebrafish thymic B cells increase relative to T cells postinvolution. We also performed RNA sequencing on D. rerio thymic and marrow lymphocytes of four novel double-transgenic lines, identifying distinct populations of immature T and B cells. Collectively, this is, to our knowledge, 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.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • B-Lymphocytes* / immunology
  • Cell Differentiation / immunology
  • Humans
  • Models, Animal
  • T-Lymphocytes / immunology
  • Thymus Gland* / cytology
  • Thymus Gland* / immunology
  • Zebrafish* / immunology