The origins of vertebrate adaptive immunity

Abstract

Adaptive immunity is mediated through numerous genetic and cellular processes that generate favourable somatic variants of antigen-binding receptors under evolutionary selection pressure by pathogens and other factors. Advances in our understanding of immunity in mammals and other model organisms are revealing the underlying basis and complexity of this remarkable system. Although the evolution of adaptive immunity has been considered to occur by acquisition of novel molecular capabilities, an increasing amount of information from new model systems suggest that co-option and redirection of preexisting systems are the major source of innovation. We combine evidence from a wide range of organisms to obtain an integrated view of the origins and patterns of divergence in adaptive immunity.With our increased understanding of mammalian adaptive immunity over the past decade, we have come to recognize the remarkable complexity of its underlying mechanisms. The core elements of this system are now mechanistically understood, such as DNA rearrangement, the generation of immune recognition diversity and the supporting cellular complexity that selects and expands cell populations expressing favourable antigen-binding receptor variants. General features of mammalian adaptive immunity -such as clonal selection, compartmental differentiation of lymphocytes, somatic hypermutation (SHM), allelic exclusion and a form of immunological memory -appeared before the emergence of the modern jawed vertebrates. Over the past several years, studies of immune receptors and immunity in a wide range of vertebrate and invertebrate species have revealed several similarities to present-day mammalian immunity and have provided insights into the evolutionary acquisition of immunological complexity 1,2 . We are within reach of important breakthroughs in our understanding of how adaptive immunity evolved in the context of an innate immune system and how these molecularly disparate systems are related and remain interdependent 3 . What has become increasingly clear is that the evolution of adaptive immunity requires the study of NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript a large range of molecular systems and that it cannot be understood from studies that are restricted to mice and humans or even from studies that use alternative vertebrate models, such as bony fish and sharks. Furthermore, we recognize that the complex set of processes that constitutes adaptive immunity can be addressed most effectively by examining its constituent steps; these include (not necessarily in order of evolutionary emergence or of equivalent complexity) the appearance of lymphocytes, the acquisition of antigen-binding receptor diversification mechanisms, the structural basis for recognition specificity, the evolution of mechanisms for receptor selection and the regulatory processes that target and attenuate immune responses. We are now in a better position to understand these essential steps in the evolutionary acquisition of ada...

Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal

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