The unexpected role of nurse shark pancreas as a secondary lymphoid organ

Secondary lymphoid organs (SLOs) provide a structured environment to facilitate interactions between low frequency antigen-specific B and T cells as well as cognate antigen displayed by antigen presenting cells (APCs), resulting in the initiation of effective adaptive immune responses. The spleen is the most evolutionary ancient SLO, emerging concurrently with adaptive immunity in an early jawed vertebrate ancestor. In mammals, the immunoprotective role of the spleen is complemented by that of other SLOs, notably a network of draining lymph nodes and gut-associated lymphoid tissue (GALT) to screen for infections throughout the host. However, lymph nodes are only present in endothermic vertebrates (ie, mammals and possibly some birds), so it is unclear how the majority of jawed vertebrate species maintain robust immune surveillance of their entire body to produce timely and efficacious antibody responses. While investigating adaptive immune responses in the nurse shark, a cartilaginous fish (Chondrichthyes) which last shared a common ancestor with other vertebrates ∼450 million yr ago, we discovered that the pancreas contains B cell follicles which are spatially distinct from the exocrine and endocrine pancreas. Furthermore, these "pancreatic B cell follicles" exhibit many of the hallmarks of B cell selection previously identified in the nurse shark spleen. Our results also demonstrate that antigen-specific antibodies are produced within the pancreas following immunization. Our study supports the designation of shark pancreas as a SLO and provides insight into how adaptive immune surveillance may function in the absence of lymph nodes.