The ancestral complement system in sea urchins

The origin of adaptive immunity in the vertebrates can be traced to the app earance of the ancestral RAG genes in the ancestral jawed vertebrate; howev er, the innate immune system is more ancient. A central subsystem within in nate immunity is the complement system, which has been identified throughou t and seems to be restricted to the deuterostomes. The evolutionary history of complement can be traced from the sea urchins (members of the echinoder m phylum), which have a simplified system homologous to the alternative pat hway, through the agnathans (hagfish and lamprey) and the elasmobranchs (sh arks and rays) to the teleosts (bony fish) and tetrapods, with increases in the numbers of complement components and duplications in complement pathwa ys. Increasing complexity in the complement system parallels increasing com plexity in the deuterostome animals. This review focuses on the simplest of the complement systems that is present in the sea urchin. Two components h ave been identified that show significant homology to vertebrate C3 and fac tor B (Bf), called SpC3 and SpBf, respectively. Sequence analysis from both molecules reveals their ancestral characteristics. Immune challenge of sea urchins indicates that SpC3 is inducible and is present in coelomic fluid (the body fluids) in relatively high concentrations, while SpBf expression is constitutive and is present in much lower concentrations. Opsonization o f foreign cells and particles followed by augmented uptake by phagocytic co elomocytes appears to be a central function for this simpler complement sys tem and important for host defense in the sea urchin. These activities are similar to some of the functions of the homologous proteins in the vertebra te complement system. The selective advantage for the ancestral deuterostom e may have been the amplification feedback loop that is still of central im portance in the alternative pathway of complement in higher vertebrates. Fe edback loop functions would quickly coat pathogens with complement leading to phagocytosis and removal of foreign cells, a system that would be signif icantly more effective than an opsonin that binds upon contact as a result oi simple diffusion. An understanding of the immune response of the sea urc hin, an animal that is a good estimator of what the ancestral deuterostome immune system was like, will aid us in understanding how adaptive immunity might have been selected for during the early evolution of the vertebrates and how it might have been integrated into the pre-existing innate immune s ystem that was already in place in those animals.