CHARACTERIZATION OF ORGANIZED SITES OF B CELL SELECTION IN THE NURSE SHARK SPLEEN
Hanover Matz, University of Waterloo
Hanover Matz1,2 and Helen Dooley1,2
1Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. 2Institute of Marine and Environmental Technology (IMET), Baltimore, MD 21231, USA
B cell clone selection and antibody affinity maturation are fundamental mechanisms of the adaptive immune response. Historically affinity maturation was believed to occur only in endothermic vertebrates, with selection taking place in germinal centers formed in the spleen and lymph nodes. However, it has since been proven that cold-blooded vertebrates are also capable of some level of affinity maturation despite lacking germinal centers and true follicular dendritic cells. This finding led us to hypothesize that a primordial B cell selection structure preceded the complex germinal centers present in mammals. Further, these structures may be retained in cartilaginous fishes, such as sharks, the oldest extant taxonomic group that possess adaptive immunity based on immunoglobulins. Through immunization studies utilizing the fluorescent antigen phycoerythrin (PE), we have identified organized sites of B cell selection in an ectothermic vertebrate, the nurse shark (Ginglymostoma cirratum). Using immunofluorescent microscopy and RNA fluorescent in situ hybridization experiments we have located, and begun to characterize, the cellular architecture of the B cell selection sites in nurse shark spleen. Our results show distinct sites where PE is presented by unknown antigen presenting cells to B cell clones expressing IgNAR (immunoglobulin new antigen receptor), a heavy-chain only immunoglobulin class and major contributor to the shark humoral adaptive response. We hypothesize that these sites facilitate selection of B cell clones undergoing somatic hypermutation, helping increase the binding affinity of the immune response. Future studies will continue to characterize the cellular and molecular underpinnings that facilitated the evolution of affinity maturation.