Variable domains and a VpreB-like molecule are present in a jawless vertebrate

Cannon, John P.; Haire, Robert N.; Pancer, Zeev; Mueller, Mathias; Skapura, Diana P.; Cooper, Max D.; Litman, Gary W.

doi:10.1007/s00251-004-0766-y

Cited by 30 publications

(15 citation statements)

References 28 publications

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“…Furthermore, no evidence is found at this stage of gene annotation for large, diversified families of V genes corresponding to Igs, TCRs, or NITRs. Jawless vertebrates do possess smaller families of receptor-type molecules containing V domains [6], whose functional roles are not understood, as well as a molecule resembling VpreB [26], a surrogate light chain that functions at an early stage in B cell differentiation in mammals [27].…”

Section: Variable Region-containing Chitin-binding Proteins (Vcbps) Amentioning

confidence: 99%

Immunoglobulin variable regions in molecules exhibiting characteristics of innate and adaptive immune receptors

et al. 2007

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The antigen combining sites of immunoglobulin (Ig) and T cell antigen receptors (TCRs), which are present in all jawed vertebrates, consist of a paired variable (V) domain heterodimer that exhibits varying degrees of germline- and extraordinarily high levels of somatically-derived variation. The near limitless variation in receptor specificity on the surface of individual lymphocytes is the basis for clonal selection in the adaptive immune response. A basic question arises as to whether or not there are other forms of immune-type receptors in vertebrates as well as in invertebrates that derive immune specificity through sequence differences in V domains. Our laboratory has discovered two such families of molecules, the novel immune-type receptors and the variable region-containing chitin-binding proteins. Both families of molecules encode V domains that share some characteristics of adaptive immune receptors but likely mediate innate functions.

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Section: Variable Region-containing Chitin-binding Proteins (Vcbps) Amentioning

confidence: 99%

Immunoglobulin variable regions in molecules exhibiting characteristics of innate and adaptive immune receptors

et al. 2007

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“…Using a V-region-directed cloning technique in lamprey lymphocytes, a single gene was identified that resembles VpreB, which encodes a surrogate BCR light-chain component that is expressed early in lymphocyte ontogeny in higher vertebrates but does not participate directly in the function of the mature BCR 92 . The lamprey VpreB-like molecule might reflect the character of an early common ancestor that might or might not have mediated an immune function 93 . In addition to the V-region-related sequences in hagfish 83 , additional immunoglobulin Vregion-related sequences that have so far been identified in lampreys include nectin and Lutheran blood-group-antigen-like genes, neither of which is related closely to BCRs or TCRs 93 .…”

Section: Anticipatory Immunity In Jawless Vertebratesmentioning

confidence: 99%

“…The lamprey VpreB-like molecule might reflect the character of an early common ancestor that might or might not have mediated an immune function 93 . In addition to the V-region-related sequences in hagfish 83 , additional immunoglobulin Vregion-related sequences that have so far been identified in lampreys include nectin and Lutheran blood-group-antigen-like genes, neither of which is related closely to BCRs or TCRs 93 . Whole-genome analysis might yet uncover BCR-or TCR-related candidates.…”

Section: Anticipatory Immunity In Jawless Vertebratesmentioning

confidence: 99%

Reconstructing immune phylogeny: new perspectives

2005

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Numerous studies of the mammalian immune system have begun to uncover profound interrelationships, as well as fundamental differences, between the adaptive and innate systems of immune recognition. Coincident with these investigations, the increasing experimental accessibility of non-mammalian jawed vertebrates, jawless vertebrates, protochordates and invertebrates has provided intriguing new information regarding the likely patterns of emergence of immune-related molecules during metazoan phylogeny, as well as the evolution of alternative mechanisms for receptor diversification. Such findings blur traditional distinctions between adaptive and innate immunity and emphasize that, throughout evolution, the immune system has used a remarkably extensive variety of solutions to meet fundamentally similar requirements for host protection.The evolutionary development of the METAZOANS was associated with the diversification of a wide range of specialized cell-surface molecules that mediate key metabolic processes, as well as provide crucial contact interfaces and carry out a broad range of other essential functions. It is not unexpected that some of these molecules also came to function as barriers to pathogenic invasion and, in doing so, began to carry out dedicated innate immune protective functions. Whereas the simplest form of protection, barrier formation, is essentially mechanical in nature, relentless pressure from genetic variation in pathogens probably drove the evolution of such innate immune protective molecules towards diversification and, in parallel, towards integration of signalling pathways to regulate cellular responses to external stimulation. However, despite the sophistication that such innate immune mediators achieved over time, their biological complexity, by definition, would be limited by genome space, so with increasing complexity of body plan and/or increasing pathogen sophistication, they could be overwhelmed. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMore than 500 million years ago, a TRANSPOSITION event, probably involving a recombinationactivating gene (RAG)-bearing element, might have given rise to the predecessors of the rearranging antigen-binding receptors of the jawed vertebrates, which encompass the vertebrate radiations that extend from the cartilaginous fish through to humans. This is considered the defining point in the emergence of RAG-mediated (conventional) adaptive immunity 1,2 , which has evolved to create a mechanism for deriving almost limitless variation from very few genes. Studies in traditional and non-traditional animal models, such as sharks, bony fish and birds, have brought this event and its ramifications for host defence into sharper focus. We can now predict much about how these rearranging antigenbinding receptors probably arose, what alternative pathways of immune-receptor gene evolution have occurred, what relationships exist between B-and T-cell-mediated immunity and natural killer (NK)-cell function, how complex immune ...

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“…Early in evolution, pro-B cells rearranged HC and LC genes at the same time, but did not produce SLC encoded by VpreB1, VpreB2 and l5 genes, a situation similar to that in chicken. Ancestral pro-B cells likely expressed a VpreB3-like gene described for chicken and sea lampreys; yet VpreB3 binds only to ER-resident HCs and is not part of surface-bound pre-BCRs [69][70][71]. The emergence of VpreB-like genes, but not l5, in sea lampreys, i.e., before the emergence of the RAG recombinase, suggests that VpreB-like genes could be the precursors of V L segments.…”

Section: Opinionmentioning

confidence: 99%