Similarities and differences in adaptive immunity between zebrafish and mammals

There is a high conservation in the structure of the T and B cell receptors for antigens. The recombination machinery, e.g. Rag-1, Rag-2 and TdT have been cloned in zebrafish, and the Rags can functionally replace mammalian Rags. T cell development proceeds in the thymus, which consists of a cortex and medulla as in mammals. To date no differences in T cell development have been demonstrated between zebrafish and mammals. However, given the absence of markers such as CD4 and CD8, we cannot firmly conclude that development and functional properties of T cell subsets in zebrafish parallel those of mammals. Zebrafish immune cells have MHC class I and II antigens, and antigen presenting cells have been described. From our transplantation experiments we know that zebrafish can rapidly reject grafts, hinting at intact NK function. In this context the recent description by Gary Litman’s group, of a new family of immune receptors, the NITR family, is of interest. These receptors have motifs that make them good candidates to be the zebrafish NK receptors.

Initial development of zebrafish B cells in the pancreas is a novelty in vertebrates. In higher vertebrates it occurs in bone marrow or the bursa of Fabricius (birds). Furthermore, class-switching does not occur in teleosts. Zebrafish only have the cµ and a c∂ constant region equivalent, and these isotypes are generated by alternative splicing. In addition, germinal centers, where class-switching and affinity maturation occur are conspicuously absent in ectotherms, including fishes. Nevertheless, sequence analysis demonstrated that hypermutation occurs in fishes, and we were able to clone zebrafish activation induced cytidine deaminase (AID), an enzyme that mediates class-switching and affinity maturation of the B cell repertoire in mammals. We are currently investigating the role of AID in zebrafish.

Lymphnodes initiate phylogenetically only in birds, and hence are absent in zebrafish. T-B cell interaction can take place in the zebrafish spleen, kidney and gut (see Figure).