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Ectothermic vertebrates, like trout, possess specialized splenic structures called MMC-associated lymphoid aggregates (M-LAs) that facilitate adaptive immune responses, functioning similarly to germinal centers found in mammals.

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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.