Is That Lymphocyte Aggregate a Tertiary Lymphoid Organ? Lymphoid Structures in Teleost Fish and the Challenges of...

Teleost fish are the most diverse of the vertebrate taxa, made up of over 30,000 different species with diverse life histories, unique immune systems and extreme physiological adaptations. Mammalian immunologists coined primary, secondary and tertiary lymphoid organs based on their developmental, anatomical and functional characteristics and such definitions are often "imposed" on other organisms. For decades, teleost fish were thought to lack lymphoid aggregates beyond those found in the primary lymphoid organs of the thymus and the head-kidney or those found in the spleen (a secondary lymphoid organ). However, over the past two decades several laboratories have uncovered the presence of lymphocyte aggregates in several anatomical locations, mostly mucosal barriers, in teleost fish. These aggregates are difficult to classify as secondary or tertiary lymphoid structures based on the current mammal-based framework. This perspective provides an overview of the latest findings in lymphocyte aggregates in teleost fish and their potential function in adaptive immunity. We proposed a revised definition for tertiary lymphoid organs (TLOs) that is relevant across a wider range of vertebrate taxa and where the lack of baseline SLO makes TLO description and functional characterization even harder. Specifically, we propose experimental paradigms where the "ectopic" nature of TLOs could be ascertained in non-model organisms.