Perspective: the variable lymphocyte receptor B system in the gut of the sea lamprey

The evolutionary origin of vertebrate adaptive immunity has been a longstanding problem in evolutionary biology. The diversified proteins that orchestrate this complex system are present throughout the jawed vertebrates but are absent in extant jawless vertebrates and invertebrates. From work initially carried out in the sea lamprey (Petromyzon marinus) and subsequently extended to other lampreys and hagfishes, we now know that, instead of immunoglobulin domain-based receptors, jawless vertebrates have leucine-rich repeat-based variable lymphocyte receptors (VLRs). Like immunoglobulins (Igs) and T cell receptors (TCRs), these proteins are somatically diversified in lymphocyte-like cells. Of the six VLR loci described in the sea lamprey (VLRA-VLRF), five are expressed exclusively as transmembrane receptors on T-like lymphocytes (VLRA and VLRC-VLRF). Here we focus on VLRB which, like jawed vertebrate immunoglobulins, is expressed both as a cell surface receptor on B-like cells and as a secreted, polyvalent VLRB antibody. Although little is known about the mucosal functions of VLR antibodies, VLRB-expressing cells diversify in gut-associated lymphopoietic tissues and are present in the gut epithelium and other regions of the intestine. We discuss what is known about VLRB and some future directions for understanding its gut-associated functions in relation to what is known in the jawed vertebrates.