Sea squirts and immune tolerance

Abstract

Transplantation specificity and protective immunity occur in both adaptive and innate branches of the vertebrate immune system. Understanding the mechanisms that underlie specificity and self-tolerance of immune function has major significance, from preventing a rejection reaction after transplantation to dissecting the causes of autoimmune disease. The core of vertebrate immunity is the ability to discriminate between highly polymorphic ligands, and this process is also found in allorecognition systems throughout the metazoa. Botryllus schlosseri is a tunicate, the modern-day descendents of the phylum that made the transition between invertebrates and vertebrates. In addition, B. schlosseri undergoes a natural transplantation reaction, which is controlled by a single, highly polymorphic locus called fuhc, reminiscent of major histocompatibility complex (MHC)-based allorecognition. The life-history characteristics of Botryllus make it an excellent model to dissect the functional and developmental mechanisms underlying allorecognition, and have the potential to reveal novel insights into issues from innate recognition strategies to the evolution of genetic polymorphism. In addition, we hypothesize that allorecognition in Botryllus must be based on conserved processes that are fundamental to all immune function: education and tolerance, or the ontogeny and maintenance of specificity.