Lymphocyte development in fish and amphibians

Recently, molecular markers such as recombination activating genes (RAG), terminal deoxynucleotidyl transferase (TdT), stem cell leukemia hematopoietic transcription factor (SCL), Ikaros and gata-binding protein (Gata)-family members have been isolated and characterized from key lower vertebrates, adding to our growing knowledge of lymphopoiesis in ectotherms. In all gnathostomes there appear to be two main embryonic locations derived from the early mesoderm, both intra- and extraembryonic, which contribute to primitive and definitive hematopoiesis based upon their differential expression of SCL, Gata-1, Gata-2 and myeloblastosis oncogene (c-myb). In teleosts, a unique intraembryonic location for hematopoietic stem cells termed the intermediate cell mass (ICM) of Oellacher appears to be responsible for primitive or definitive hematopoiesis depending upon the species being investigated. In Xenopus, elegant grafting studies in combination with specific molecular markers has led to a better definition of the roles that ventral blood islands and dorsal lateral plate play in amphibian hematopoiesis, that of primitive and definitive lymphopoiesis. After the early embryonic contribution to hematopoiesis, specialized tissues must assume the role of providing the proper microenvironment for T and B-lymphocyte development from progenitor stem cells. In all gnathostomes, the thymus is the major site for T-cell maturation as evidenced by strong expression of developmental markers such as Ikaros, Rag and TdT plus expression of T-cell specific markers such as T-cell receptor beta and lck. In this respect, several zebrafish mutants have provided new insights on the development of the thymopoietic environment. On the other hand, the sites for B-cell lymphopoiesis are less clear among the lower vertebrates. In elasmobranchs, the spleen, Leydig's organ and the spiral valve may all contribute to B-cell development, although pre-B cells have yet to be fully addressed in fish. In teleosts, the kidney is undeniably the major source of B-cell development based upon functional, cellular and molecular indices. Amphibians appear to use several different sites (spleen, bone marrow and/or kidney) depending upon the species in question.