Cold-blooded vertebrates evolved organized germinal center-like structures

Area of Science:

• Immunology
• Comparative Biology
• Evolutionary Medicine

Background:

• Germinal centers (GCs) and secondary lymphoid microstructures (SLMs) are traditionally associated with endothermic species.
• Ectothermic vertebrates mount adaptive immune responses but lack apparent SLMs, leaving the induction sites of these responses unclear.
• Understanding immune response induction in ectotherms is crucial for evolutionary insights into adaptive immunity.

Purpose of the Study:

• To investigate the cellular and molecular mechanisms underlying adaptive immune responses in ectothermic fish.
• To identify potential structures analogous to GCs in cold-blooded vertebrates.
• To elucidate the role of splenic microstructures in adaptive immunity of ectotherms.

Main Methods:

• Infection of teleost fish (trout) with Ichthyophthirius multifiliis (Ich).
• Identification and characterization of splenic lymphoid aggregates associated with melanomacrophage centers (M-LAs).
• Analysis of B cell proliferation, antigen specificity, IgM heavy chain CDR3 repertoire, activation-induced cytidine deaminase expression, apoptosis, and somatic hypermutation within M-LAs.

Main Results:

• Formation of M-LAs containing proliferating IgM+ B cells and CD4+ T cells, adjacent to splenic MMCs.
• M-LAs harbor antigen-specific B cells, demonstrating clonal expansion and somatic hypermutation of Ig genes.
• M-LAs exhibit GC-like functions, including B cell activation, proliferation, apoptosis, and Ig gene diversification.

Conclusions:

• Ectothermic vertebrates have evolved organized SLMs (M-LAs) with functions analogous to mammalian GCs.
• M-LAs represent primordial secondary lymphoid structures crucial for adaptive immune responses in ectotherms.
• The findings suggest conserved evolutionary mechanisms for SLM development and function across vertebrates.