Do ectothermic vertebrates have a home in which to affinity mature their antibody responses?

Abstract

There has been a longstanding question of whether affinity maturation occurs in ectotherms, and if it does, where in tissues this happens. Although cold-blooded vertebrates (ectotherms) lack histologically discernible germinal centers, they have a fully functional Ig gene mutator enzyme (activation-induced cytidine deaminase: AID or Aicda). Protein and Ig cDNA transcript analyses provide evidence that ectotherms can, under certain conditions, demonstrate antibody affinity maturation, and somatic hypermutation of their Ig genes during secondary immune responses. Here, we review the evidence for antibody affinity maturation and somatic hypermutation of Ig V(D)J exons. We argue that past evidence of long-term intact antigen retention, and recent studies of in situ expression of AID transcripts, point to fish melanomacrophage clusters as sites functionally analogous to a germinal center. Recent work in zebrafish provides a way forward to test these predictions through V(D)J repertoire analyses on isolated, intact melanomacrophage clusters. This work has implications not only for vaccine use in aquaculture, but also for antibody affinity maturation processes in all ectothermic vertebrates.

Keywords: Activation-induced cytidine deaminase; Amphibian; Antibodies; Antibody affinity maturation; Ectotherms; Fish; Germinal center; Immunoglobulins; Review; Shark.