Investigating the functional roles of TNFSF13 family members in Cartilaginous Fishes

Abstract

Abstract The TNFSF13 cytokines BAFF and APRIL along with their cognate receptors BAFFR, TACI, and BCMA play critical parts in the development, function, and maintenance of B cells in mammals. Despite the well-studied roles that BAFF and APRIL play in the immune systems of higher vertebrates, their evolutionary history and functions in non-mammalian organisms are not well understood. Recently, our lab has demonstrated that collectively the TNFSF is evolutionarily ancient, with most of its members having evolved over 450 million years ago in the jawed vertebrate ancestor. Interestingly, we found that despite the evolutionary ancient position of cartilaginous fishes, their repertoire of TNFSF is just as complex as higher vertebrates with evidence of lineage specific TNFSF members that are absent in more evolutionary recent taxa. Specifically, cartilaginous fishes possess two additional TNFSF13 family members, namely BALM (TNFSF13C) and a retrotransposed duplicate of BAFF (iBAFF). Thus, cartilaginous fishes possess four TNFSF13 members whose functional roles remain unexplored. Here we demonstrate the tissue specific expression of BAFF, iBAFF, BALM, and APRIL, as well as their anticipated receptors BAFFR, TACI, and BCMA in the nurse shark. Additionally, we explore receptor-ligand interactions using a yeast surface display assay aiming to understand the role(s) each plays in the development and maintenance of shark B cells. Such information is key to understanding the evolutionary history of this key cytokine family.