Criscitiello, M. F. & Flajnik, M. F. Four primordial immunoglobulin light chain isotypes, including λ and κ, identified in the most primitive living jawed vertebrates. Eur. J. Immunol. 37, 2683-2694

Department of Microbiology and Immunology , University of Maryland, Baltimore, Baltimore, Maryland, United States
European Journal of Immunology (Impact Factor: 4.03). 11/2007; 37(10):2683-94. DOI: 10.1002/eji.200737263
Source: PubMed


The discovery of a fourth immunoglobulin (Ig) light (L) chain isotype in sharks has revealed the origins and natural history of all vertebrate L chains. Phylogenetic comparisons have established orthology between this new shark L chain and the unique Xenopus L chain isotype sigma. More importantly, inclusion of this new L chain family in phylogenetic analyses showed that all vertebrate L chains can be categorized into four ancestral clans originating prior to the emergence of cartilaginous fish: one restricted to elasmobranchs (sigma-cart/type I), one found in all cold-blooded vertebrates (sigma/teleost type 2/elasmobranch type IV), one in all groups except bony fish (lambda/elasmobranch type II), and one in all groups except birds (kappa/elasmobranch type III/teleost type 1 and 3). All four of these primordial L chain isotypes (sigma, sigma-cart, lambda and kappa) have maintained separate V region identities since their emergence at least 450 million years ago, suggestive of an ancient physiological distinction of the L chains. We suggest that, based upon unique, discrete sizes of complementarity determining regions 1 and 2 and other features of the V region sequences, the different L chain isotypes arose to provide different functional conformations in the Ig binding site when they pair with heavy chains.

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Available from: Mike Criscitiello, Sep 29, 2014
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    • "A close examination of V L based on its phylogenetic relationships , CDR lengths and RSS orientation , recognized four ancestral V L clades that were maintained throughout the vertebrates ( Criscitiello and Flajnik , 2007 ) . A distinct variant of the s isotype , which was named s‐cart ( for cartilaginous fish ) , has been identified only in the shark ( Criscitiello and Flajnik , 2007 ) . The organization of the light chain loci among the vertebrates is not as definitive or diagnostic as for the heavy chain loci and can consist of cluster‐type , translocon‐type or perhaps other variations ( Hsu and Criscitiello , 2006 ) . "
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    ABSTRACT: We have analyzed the available genome and transcriptome resources from the coelacanth in order to characterize genes involved in adaptive immunity. Two highly distinctive IgW-encoding loci have been identified that exhibit a unique genomic organization, including a multiplicity of tandemly repeated constant region exons. The overall organization of the IgW loci precludes typical heavy chain class switching. A locus encoding IgM could not be identified either computationally or by using several different experimental strategies. Four distinct sets of genes encoding Ig light chains were identified. This includes a variant sigma-type Ig light chain previously identified only in cartilaginous fishes and which is now provisionally denoted sigma-2. Genes encoding α/β and γ/δ T-cell receptors, and CD3, CD4, and CD8 co-receptors also were characterized. Ig heavy chain variable region genes and TCR components are interspersed within the TCR α/δ locus; this organization previously was reported only in tetrapods and raises questions regarding evolution and functional cooption of genes encoding variable regions. The composition, organization and syntenic conservation of the major histocompatibility complex locus have been characterized. We also identified large numbers of genes encoding cytokines and their receptors, and other genes associated with adaptive immunity. In terms of sequence identity and organization, the adaptive immune genes of the coelacanth more closely resemble orthologous genes in tetrapods than those in teleost fishes, consistent with current phylogenomic interpretations. Overall, the work reported described herein highlights the complexity inherent in the coelacanth genome and provides a rich catalog of immune genes for future investigations. J. Exp. Zool. (Mol. Dev. Evol.) 9999B: 1-26, 2014. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Sep 2014 · Journal of Experimental Zoology Part B Molecular and Developmental Evolution
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    • "The emerging classification system currently differentiates between four ancestral clans: kappa (κ/elasmobranch type III/NS4/ Teleost L1, L3, F, G/Xenopus r), lambda (λ/elasmobranch type II), sigma (σ/teleost L2/ elasmobranch type IV), and sigma cart (σ-cart). Criscitiello and Flajnik (2007) have proposed an IgL classification system based on criteria of sequence homology, and the spacing of heptamer and nonamers of recombination signal sequences (RSS). In addition, the genomic configuration of IgL gene segments and the length of the complementary determining regions (CDR) of corresponding V L gene segments support a syntenic approach to IgL classification. "
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    ABSTRACT: The gene segments encoding antibodies have been studied in many capacities and represent some of the best-characterized gene families in traditional animal disease models (mice and humans). To date, multiple immunoglobulin light chain (IgL) isotypes have been found in vertebrates and it is unclear as to which isotypes might be more primordial in nature. Sequence data emerging from an array of fish genome projects is a valuable resource for discerning complex multigene assemblages in this critical branch point of vertebrate phylogeny. Herein, we have analyzed the genomic organization of medaka (Oryzias latipes) IgL gene segments based on recently released genome data. The medaka IgL locus located on chromosome 11 contains at least three clusters of IgL gene segments comprised of multiple gene assemblages of the kappa light chain isotype. These data suggest that medaka IgL gene segments may undergo both intra- and inter-cluster rearrangements as a means to generate additional diversity. Alignments of expressed sequence tags to concordant gene segments which revealed each of the three IgL clusters are expressed. Collectively, these data provide a genomic framework for IgL genes in medaka and indicate that Ig diversity in this species is achieved from at least three distinct chromosomal regions.
    Full-text · Article · Feb 2013 · Immunogenetics
    • "Four immunoglobulin light chain (IgL) isotypes have been described in teleosts: L1, L2, L3, and λ (Edholm et al., 2009; Bao et al., 2010). A recent comprehensive phylogenetic analysis of vertebrate VL and CL sequences suggested that fish L1 and L3 chains are κ orthologous (Criscitiello and Flajnik, 2007), and fish L2 are orthologs of Xenopus σ (Partula et al., 1996). The current general classification of IgL from all vertebrates distinguishes four clans based on phylogenetic relationships: κ (mammalian κ, elasmobranch Type III, Teleost L1, and L3, Xenopus ρ), λ (mammalian λ, elasmobranch type II), σ (Xenopus σ, teleost L2, elasmobranch type IV), and σ cart (σ-cart, that is restricted to elasmobranch). "
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    ABSTRACT: With lymphoid tissue anatomy different than mammals, and diverse adaptations to all aquatic environments, fish constitute a fascinating group of vertebrate to study the biology of B cell repertoires in a comparative perspective. Fish B lymphocytes express immunoglobulin (Ig) on their surface and secrete antigen-specific antibodies in response to immune challenges. Three antibody classes have been identified in fish, namely IgM, IgD, and IgT, while IgG, IgA, and IgE are absent. IgM and IgD have been found in all fish species analyzed, and thus seem to be primordial antibody classes. IgM and IgD are normally co-expressed from the same mRNA through alternative splicing, as in mammals. Tetrameric IgM is the main antibody class found in serum. Some species of fish also have IgT, which seems to exist only in fish and is specialized in mucosal immunity. IgM/IgD and IgT are expressed by two different sub-populations of B cells. The tools available to investigate B cell responses at the cellular level in fish are limited, but the progress of fish genomics has started to unravel a rich diversity of IgH and immunoglobulin light chain locus organization, which might be related to the succession of genome remodelings that occurred during fish evolution. Moreover, the development of deep sequencing techniques has allowed the investigation of the global features of the expressed fish B cell repertoires in zebrafish and rainbow trout, in steady state or after infection. This review provides a description of the organization of fish Ig loci, with a particular emphasis on their heterogeneity between species, and presents recent data on the structure of the expressed Ig repertoire in healthy and infected fish.
    No preview · Article · Feb 2013 · Frontiers in Immunology
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