Immunoglobulin Isotypes: Structure, Function, and Genetics

Bengtén, Eva; Wilson, Melanie; Miller, Norman W.; Clem, L. William; Pilström, Lars; Warr, Gregory W.

doi:10.1007/978-3-642-59674-2_9

Cited by 77 publications

(56 citation statements)

References 132 publications

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“…However, a lack of data from key phylogenetic groups as well as no identifiable distinct functions for different IgL isotypes have made assignation of L chain isotypes controversial. Three criteria have been considered: amino acid identity, gene organization, and heptamer and nonamer spacing in the RSS (either 12 or 23 base pairs) [5]. Gene organization has recently been informative for resolving relationships among teleost (i.e., bony fish) L chain isotypes [6].…”

Section: Introductionmentioning

confidence: 99%

Four primordial immunoglobulin light chain isotypes, including λ and κ, identified in the most primitive living jawed vertebrates

Criscitiello

Flajnik

2007

Eur J Immunol

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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 r. 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 (r-cart/type I), one found in all cold-blooded vertebrates (r/teleost type 2/elasmobranch type IV), one in all groups except bony fish (k/elasmobranch type II), and one in all groups except birds (j/elasmobranch type III/teleost type 1 and 3). All four of these primordial L chain isotypes (r, r-cart, k and j) 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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Section: Introductionmentioning

confidence: 99%

Four primordial immunoglobulin light chain isotypes, including λ and κ, identified in the most primitive living jawed vertebrates

Criscitiello

Flajnik

2007

Eur J Immunol

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“…A typical Ig molecule consists of two H and two L chains, with the H and L chains being encoded in separate IGH 5 and IGL loci (2). The H and L polypeptides are typically covalently linked by disulfide bonds formed by positionally conserved cysteine residues; however, noncovalent interactions alone are sufficient to hold L and H chains together, as observed for human IgA2m (1) and Igs of Rana catesbeiana (3,4).…”

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confidence: 99%

“…The first is the question of how the genes encoding the H chains arose, one from the other, and how their subsequent evolutionary divergence permitted the acquisition of novel Ab functions including transport and secretion into external body fluids such as mucus and milk, or the mediation of allergic reactions. In summary, first, IgM is the only class of Ab that is expressed in all species of jawed vertebrates (1,2,5). Second, IgD is a class of Ab that is probably as ancient as IgM, existing in elasmobranchs as a class that was originally named IgW but is now recognized as a homolog of IgD (6).…”

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Expression of IgM, IgD, and IgY in a Reptile, Anolis carolinensis

Wei

Ren

et al. 2009

The Journal of Immunology

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The reptiles are the last major group of jawed vertebrates in which the organization of the IGH locus and its encoded Ig H chain isotypes have not been well characterized. In this study, we show that the green anole lizard (Anolis carolinensis) expresses three Ig H chain isotypes (IgM, IgD, and IgY) but no IgA. The presence of the δ gene in the lizard demonstrates an evolutionary continuity of IgD from fishes to mammals. Although the germline δ gene contains 11 CH exons, only the first 4 are used in the expressed IgD membrane-bound form. The μ chain lacks the cysteine in CH1 that forms a disulfide bond between H and L chains, suggesting that (as in IgM of some amphibians) the H and L polypeptide chains are not covalently associated. Although conventional IgM transcripts (four CH domains) encoding both secreted and membrane-bound forms were detected, alternatively spliced transcripts encoding a short membrane-bound form were also observed and shown to lack the first two CH domains (VDJ-CH3-CH4-transmembrane region). Similar to duck IgY, lizard IgY H chain (υ) transcripts encoding both full-length and truncated (IgYΔFc) forms (with two CH domains) were observed. The absence of an IgA-encoding gene in the lizard IGH locus suggests a complex evolutionary history for IgA in the saurian lineage leading to modern birds, lizards, and their relatives.

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“…The E enhancer, located in the J H -C intron, is arguably the most important; not only is it required for expression of the rearranged IgH locus, but it also plays an important role in the processes of V H -D-J H recombination and somatic hypermutation and is not deleted by any of the recombination processes that occur during B cell development. The IgH locus of the channel catfish, the best-established model for the teleost immune system, is less complex than that of mammals; only two classes of immunoglobulin (IgM and IgD) are produced through alternative processing of the primary transcript from the IgH locus (7,8). Class switching by chromosomal recombination does not occur in teleost fish.…”

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confidence: 99%

An IgH Enhancer That Drives Transcription through Basic Helix-Loop-Helix and Oct Transcription Factor Binding Motifs

Cioffi¹,

Middleton²,

Wilson³

et al. 2001

Journal of Biological Chemistry

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The transcriptional enhancer (E3) of the IgH locus of the channel catfish, Ictalurus punctatus, shows strong B cell-specific activity and differs from the mammalian E enhancer in both location and structure. It occurs between the and ␦ genes and contains numerous transcription factor binding sites, predominantly octamer and E5 motifs of consensus and variant sequences. It lacks the classical A-E3(CBF)-B core array of binding motifs seen within mammalian IgH E enhancers. To determine the functionally important motifs, a series of mutant enhancers was created using sequence-targeted polymerase chain reaction. Whereas the mutation of consensus and variant octamer motifs (individually or in multiples) decreased enhancer function, mutation of a single consensus E5 motif destroyed the function of this enhancer in mammalian plasmacytomas. Mutation of this consensus E5 site, combined with mutations of certain octamer sites, destroyed function in catfish B cells. Experiments using artificial enhancers containing multimers of motifs or short regions of the native enhancer suggested that the minimal E3 enhancer (a) contains a consensus E5 site and two octamer sites, (b) is B cell-specific, and (c) is active across species. The dependence of an Ig enhancer on sites that bind basic helix-loop-helix and Oct transcription factors has not previously been observed and confirms large differences in structure and function between fish and mammalian IgH enhancers.Teleost (bony) fishes represent the evolutionary lineage that is most divergent from mammals yet still shares with them the organization of the IgH 1 locus. In both mammals and bony fish the V H , 1 D, J H , and C gene segments are in tandem arrays, also known as the translocon arrangement (1). Within the IgH locus of mammals, there are six described enhancers, required for the processes of V-D-J recombination, class switching, somatic hypermutation, and expression of the functionally rearranged locus (2-4). These enhancers are both internal to and 3Ј of the locus and are tightly regulated in function at different stages of B cell development (5, 6). The E enhancer, located in the J H -C intron, is arguably the most important; not only is it required for expression of the rearranged IgH locus, but it also plays an important role in the processes of V H -D-J H recombination and somatic hypermutation and is not deleted by any of the recombination processes that occur during B cell development. The IgH locus of the channel catfish, the best-established model for the teleost immune system, is less complex than that of mammals; only two classes of immunoglobulin (IgM and IgD) are produced through alternative processing of the primary transcript from the IgH locus (7,8). Class switching by chromosomal recombination does not occur in teleost fish. The single identified enhancer (E3Ј) driving IgH transcription is located in the -␦ intergenic region (9). The structure and organization of E and E3Ј differ greatly. Mammalian E is ϳ500 bp in length and contains several DNA binding mot...

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Immunoglobulin Isotypes: Structure, Function, and Genetics

Cited by 77 publications

References 132 publications

Four primordial immunoglobulin light chain isotypes, including λ and κ, identified in the most primitive living jawed vertebrates

Four primordial immunoglobulin light chain isotypes, including λ and κ, identified in the most primitive living jawed vertebrates

Expression of IgM, IgD, and IgY in a Reptile, Anolis carolinensis

An IgH Enhancer That Drives Transcription through Basic Helix-Loop-Helix and Oct Transcription Factor Binding Motifs

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