Antibodies of sharks: revolution and evolution

The combinatorial immune response is restricted to jawed vertebrates with c artilaginous fishes being the lowest extant species to have the mechanism f or diversification and an extensive panoply of immunoglobulins, T-cell rece ptors and MHC products. Here, we review the molecular events of the "big ba ng" or rapid evolutionary appearance of the functionally complete combinato rial immune system coincident with the appearance of ancestral jawed verteb rates, suggesting that this event was catalyzed by horizontal transfer of D NA processing systems. We analyze the nature and extent of variable and con stant domain diversity among the distinct immunoglobulin sets of carcharhin e sharks focusing upon the lambda-like light chains and the mu and omega he avy chains. The detection and isolation of natural antibodies from the bloo d of unimmunized sharks illustrates a surprising range of recognition speci ficities and the existence of polyspecificity suggests that the antibody-fo rming system of sharks offers unique opportunities for studies of immunolog ical regulation. Although the homologies between shark and mammalian immuno globulins are unequivocal, major differences in segmental gene organization present challenges to our understanding of basic immunological phenomena s uch as clonal restriction.