Antibodies of sharks: revolution and evolution

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Abstract
Summary: The combinatorial immune response is restricted to jawed vertebrates with cartilaginous fishes being the lowest extant species to have the mechanism for diversification and an extensive panoply of immuno‐globulins, T‐cell receptors and MHC products. Here, we review the molecular events of the “big bang” or rapid evolutionary appearance of the functionally complete combinatorial immune system coincident with the appearance of ancestral jawed vertebrates, suggesting that this event was catalyzed by horizontal transfer of DNA processing systems. We analyze the nature and extent of variable and constant domain diversity among the distinct immunoglobulin sets of carcharhine sharks focusing upon the X‐like light chains and the u and CO heavy chains. The detection and isolation of natural antibodies from the blood of unimmunized sharks illustrates a surprising ratige of recognition specificities and the existence of polyspecificity suggests that the antibody‐forming system of sharks offers unique opportunities for studies of immunological regulation. Although the homologies between shark and mamma an immunoglobulins are unequivocal, major differences in segmental gene organization present challenges co our understanding of basic immunological phenomena such as clonal restriction.

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