THE TNF SUPERFAMILY LIGAND AND RECEPTOR REPERTOIRE OF CARTILAGINOUS FISHES
Helen Dooley, University of Aberdeen & University of Maryland School of Medicine
Rita Pettinello1, Anthony K. Redmond1,2, Helen Dooley1,3
1School of Biological Sciences and 2Centre for Genome-Enabled Biology & Medicine, University of Aberdeen, Aberdeen AB24 2TZ, United Kingdom.
3Dept. Microbiology & Immunology, University of Maryland School of Medicine, Institute of Marine & Environmental Technology (IMET), Baltimore MD 21202. USA.
The tumor necrosis factor superfamily (TNFSF) cytokines BAFF (TNFSF13b) and APRIL (TNFSF13) regulate mammalian B cell development, survival, and function through interaction with their shared receptors BAFF-R (TNFRSF13c), BCMA (TNFRSF17) and TACI (TNFRSF13b). BAFF is critical for the development and maintenance of antigennaïve B cells, controlling the size and self-reactivity of the B cell pool. APRIL, in contrast, regulates the long-term survival of antigen-experienced plasma cells and homeostasis of peritoneal cavity B1 cells. Together these two ligands direct antibody-mediated protection in mammals. While completing a survey of the TNFSF and TNFRSF repertoires of cartilaginous fishes we identified orthologs of the receptors BAFF-R, BCMA, and TACI. In addition to the BAFF orthologue previously identified by our group, we also identified an APRIL orthologue in cartilaginous fishes. Unexpectedly, we also found a third TNFSF13-family ligand, BALM (proposed TNFSF13c), previously thought to be a bony fish-specific TNFSF member. A comprehensive phylogenetic analysis, incorporating the new cartilaginous fish sequences, reveals that an APRIL-like molecule was most likely the founding member of the TNFSF13 family, being present in the ancestor of all vertebrates. Further, that BALM was present when immunoglobulin-expressing B cells emerged in the ancestor of jawed vertebrates; while retained by all extant fishes (cartilaginous, bony, and lobe-finned), BALM was secondarily lost in the common tetrapod ancestor. Our results will be discussed in the context of vertebrate B cell evolution.