A large section of the gene locus encoding human immunoglobulin variable regions of the Kappa type is duplicated

Pech, Michael; Smola, Hans; Pohlenz, Hans-Dieter; Straubinger, Bernhard; Gerl, Rita; Zachau, Hans G.

doi:10.1016/0022-2836(85)90001-4

Cited by 80 publications

(38 citation statements)

References 32 publications

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“…We ordered the porcine J segments like those in humans; the location of JX (derived from a cosmid) remains unknown. It is possible that part of the locus has been duplicated as in humans, and JX may come from a duplicated region not in the genomic DNA segment we recovered (32,33). The alignment of the J segments in the locus agrees with the alignment of J1 through J5 seen in human, horse, rabbit, mouse, and rat.…”

Section: Discussionsupporting

confidence: 68%

Antibody Repertoire Development in Fetal and Neonatal Pigs. VII. Characterization of the Preimmune κ Light Chain Repertoire

Butler

Wertz

Sun

et al. 2004

The Journal of Immunology

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Combinatorial diversity is highly restricted in the preimmune porcine H chain repertoire compared with that in humans and mice. This raised the question of whether similar restriction characterized the preimmune L chain repertoire. In this study we present evidence that >90% of all expressed Vκ genes in the porcine preimmune repertoire belong to three subfamilies of Vκ genes that share 87% sequence similarity with human IGKV2. This porcine Vκ family also shares sequence similarity with some, but not all, Vκ genes from sheep. Hybridization with sperm DNA and sequence analyses of polynucleotides from overlapping bacterial artificial chromosome clones suggest swine possess ∼60 IGVK2 genes. The latter method also revealed that certain IGKV2 subfamilies are not expressed in the preimmune repertoire. Six members of an IGVK1 family were also expressed as part of the preimmune repertoire, and these shared 87% sequence similarity with human IGVK1. Five Jκ segments, complete with recombination signal sequences and separated by ∼300 nt, were identified ∼3 kb upstream of a single Cκ. Surprisingly, Jκ2 accounted for >90% of all framework region 4 sequences in the preimmune repertoire. These findings show that swine use ∼10 IGVK2 genes from three of six subfamilies and preferentially one Jκ segment to generate their preimmune κ repertoire. These studies, like those of porcine Ig constant regions and MHC genes, also indicate unexpected high sequence similarity with their human counterparts despite differences in phylogeny and the mechanism of repertoire diversification.

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Section: Discussionsupporting

confidence: 68%

Antibody Repertoire Development in Fetal and Neonatal Pigs. VII. Characterization of the Preimmune κ Light Chain Repertoire

Butler

Wertz

Sun

et al. 2004

The Journal of Immunology

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“…VH families may have then evolved by more recent divergence including, perhaps, expansions and contractions . There is, in fact, evidence for both a large duplication within the human IgVx locus (50) and for smaller, incremental changes within mouse VH gene families (51).…”

Section: Resultsmentioning

confidence: 99%

The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters.

Brodeur¹,

Osman²,

Mackle³

et al. 1988

The Journal of Experimental Medicine

108

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Studies ofIg gene structure and organization during the past decade have illuminated the central mechanisms of antibody diversification: the somatic rearrangement and reassortment of multiple gene segments, junctional flexibility, and point mutation . The inherited set of Ig gene segments provides a diversified genetic basis upon which these dynamic processes operate during ontogeny. Thus, the composition of these germline genes imposes a major influence on the development of the antibody repertoire.The present study examines the germline content and organization of the mouse heavy chain variable region genes (V genes) . We set out to analyze the locus in sufficient detail and resolution to provide the basis for determining the extent of inherited Vgene diversity, the evolution ofthe germline repertoire, and any functional consequences of the physical arrangement of the V gene segments .The mouse Igh locus consists of at least 100-200 V genes (1-3). V gene families, defined by nucleotide sequence relationships, comprise distinct sets of highly related V genes that can be identified by hybridization using prototypic V gene probes . This classification of V gene families (l, 4) has provided a useful framework for the study of germline V gene content, polymorphism, and utilization (1-7). Whereas the general organization of the Igh locus is 5'-V HDJ .-C -3' (8, 9), previous studies of V gene family organization have resulted in partial, relatively low resolution maps lacking consistency between reports (10-12)."Deletion mapping" takes advantage of the fact that V, gene rearrangements result in the deletion of DNA originally separating the rearranged V gene segment and the DJ .-CH region (13). We have constructed a panel of 32 pre-B cell lines, most of which have rearranged V, genes on both chromosomes. Since these cell lines were derived from Fi mice heterozygous at the Igh locus, V, gene deletions can be identified using RFLPs. V, gene analyses of 51 independently rearranged chromosomes are consistent with a single V, gene map order of nine V, gene families. The genomic stability of these cell lines and consistent deletion profiles of all 51 rearranged loci provide a high resolution V gene map that has compelling experimental support.

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“…In particular, the Fab 5H2 ␥1 heavy- chain and light-chain sequences had 89 and 94% sequence similarity to the human germ line IgG gene homologues, excluding the CD3 region (48,60). Furthermore, in the C H 1 or C L region, there was only one amino acid (or approximately 1.0%) difference between chimpanzee and human sequences (data not shown) (16,59).…”

Section: Discussionmentioning

confidence: 95%

Identification of Chimpanzee Fab Fragments by Repertoire Cloning and Production of a Full-Length Humanized Immunoglobulin G1 Antibody That Is Highly Efficient for Neutralization of Dengue Type 4 Virus

Men

Yamashiro

Goncalvez

et al. 2004

J Virol

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A safe and effective dengue vaccine is still not available. Passive immunization with monoclonal antibodies from humans or nonhuman primates represents an attractive alternative for the prevention of dengue virus infection. Fab monoclonal antibodies to dengue type 4 virus (DENV-4) were recovered by repertoire cloning of bone marrow mRNAs from an immune chimpanzee and analyzed for antigen binding specificity, V H and V L sequences, and neutralizing activity against DENV-4 in vitro. Fabs 5A7, 3C1, 3E4, and 7G4 were isolated from a library constructed from a chimpanzee following intrahepatic transfection with infectious DENV-4 RNA. Fabs 5H2 and 5D9, which had nearly identical V H sequences but varied in their V L sequences, were recovered from a library constructed from the same chimpanzee after superinfection with a mixture of DENV-1, DENV-2, and DENV-3. In radioimmunoprecipitation, Fab 5A7 precipitated only DENV-4 prM, and Fabs 3E4, 7G4, 5D9, and 5H2 precipitated DENV-4 E but little or no prM. Among the arthropod-borne flaviviruses, the four dengue virus serotypes (dengue type 1 virus [DENV-1], DENV-2, DENV-3, and DENV-4) that constitute a serologically distinct subgroup are most important in terms of human morbidity and geographic distribution. Dengue viruses cause dengue outbreaks and major epidemics in most tropical and subtropical areas where Aedes albopictus and Aedes aegypti mosquitos are abundant. Dengue virus infection produces fever, rash, and joint pain in humans. A more severe and life-threatening form of dengue, characterized by hemorrhagic fever and hemorrhagic shock, has occurred with increasing frequency in Southeast Asia and Central and South America, where all four dengue virus serotypes circulate. The underlying cause of severe dengue remains controversial (23,53). An association of severe dengue with increased viral replication has been reported recently (61). A safe and effective vaccine against dengue is currently not available.The dengue virus contains a positive-strand RNA genome coding for a polyprotein that is cleaved co-and posttranslationally by a combination of cellular and viral proteases to generate the individual viral proteins (9,19,40). Dengue virus prM and E structural proteins and nonstructural NS1 protein are glycosylated. The prM glycoprotein is further cleaved by the cellular enzyme furin following viral assembly, generating M, which is present in the mature virus (58). Flavivirus prM and E form heterodimers, which are assembled into viral particles during infection (62). In this manner, the prM serves to protect the functional integrity of E from acid-induced conformational change (26,31). The E glycoprotein is responsible for cell attachment, possibly mediated by a receptor, and for fusion with the cell membranes following viral entry.Mouse monoclonal antibodies against the dengue viruses have been valuable for dengue virus serotype determination (20,27). Studies in which monoclonal antibodies were used against dengue virus and other flaviviruses have also provided valuable...

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A large section of the gene locus encoding human immunoglobulin variable regions of the Kappa type is duplicated

Cited by 80 publications

References 32 publications

Antibody Repertoire Development in Fetal and Neonatal Pigs. VII. Characterization of the Preimmune κ Light Chain Repertoire

Antibody Repertoire Development in Fetal and Neonatal Pigs. VII. Characterization of the Preimmune κ Light Chain Repertoire

The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters.

Identification of Chimpanzee Fab Fragments by Repertoire Cloning and Production of a Full-Length Humanized Immunoglobulin G1 Antibody That Is Highly Efficient for Neutralization of Dengue Type 4 Virus

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