Code Blue: Nurse Cells Can Resuscitate Lymphocyte Receptors in Nurse Shark Thymus by Secondary Rearrangement
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AbstractThe thymus is the most conserved primary lymphoid organ present, in some form, in mammals to all the way back in lamprey. It is composed of a densely-packed outer cortex and an exiguous inner medulla. The thymus functions to provide a microenvironment conducive to T lymphocyte maturation and receptor repertoire formation. Sharks are situated at a pivotal location in evolutionary immunology. They are the oldest vertebrates to have similar adaptive immune characteristics to mammals. Shark lymphocyte antigen receptors are diversified by V(D)J recombination via RAG and heavy chain class switch recombination catalyzed by AID. Somatic hypermutation occurs in both B and T cell antigen receptors of shark, mediated by AID as well. Shark T cell receptors also employ antibody-like NARTCR and IgHV components. Looking at the oldest lymphoid tissue in the oldest vertebrate ancestor with adaptive characteristics similar to mammals will yield important information on the evolution of the adaptive immune response as it relates to T lymphocytes. Nurse cells are cortical thymic epithelial cells that play an important role in selection of functional T cells during the maturation process. Nurse cells have been shown, in mice, to surround non-functional T cells in order to allow them to reconfigure their receptors and attempt selection another time via RAG and/or AID. Through the use of immunohistochemistry and in situ hybridization, we will investigate whether nurse cells provide a microenvironment for shark thymocyte receptor revision in sharks as in mammals.
