| Cartilaginous fish are the oldest vertebrate class possessing an adaptive immune system typified by major histocompatibility complex (MHC) T cell receptor and immunoglobulin (Ig). Three heavy chain classes have been identified in cartilaginous fish, bona fide IgM, IgNAR, thought to be important for secondary responses, and IgW. In most vertebrates the immune repertoire expressed early in development has innate features, such as antibody variable regions in germline configuration with little somatic modification, produced by a specialized B lymphocyte subset. We have identified a fourth class of Ig, IgMinnate (in) in the nurse shark (Ginglymostoma cirratum ) expressed preferentially in neonatal primary and secondary lymphoid tissues with a germline, (germline-joined) non-diverse variable region, and at maturity expressed only in the epigonal organ, the bone marrow equivalent. IgMin heavy chain associates covalently with light chains and is most similar in sequence to pH chains, but like mammalian IgG has only three constant domains; deletion of the ancestral IgM C2 domain defines both IgG and IgMin, demonstrating molecular convergence.; The adult nurse shark spleen has well-defined, well-vascularized white pulps populated by a central "T cell" zone filled with a network of dendritic cells (DC) and rare plasma cells, surrounded by a B cell zone containing IgM+ or IgNAR+ and MHC class II + B cells. Newborn splenic white pulp matures into B and T cell zones with a delay of MHC class II expression on B cells, and delay in T cell and DC movement into the white pulp, all comparable to mammalian development. IgNAR+ B cells are also delayed in development, concurrent with arrival of T cells and DCs. The neonatal epigonal organ is the major site of B lymphopoiesis based on the presence of transmembrane IgM, developing B cells, and RAG1 and TdT expression.; Shark immunization studies established the antigen was transported into the splenic red pulp by macrophages after one week and by four weeks was moved into the white pulp "T cell" zone and presented on the cell surface of putative DCs. Clusters of IgNAR+ secretory cells in the same "T cell" zones are hypothesized to be sites of somatic mutation and selection, perhaps analogous to mammalian germinal centers. |
