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Chromosomal localization of the human IGL locus at 22q11.2. The vertical line indicates the localization of the IGL locus at 22q11.2. The arrow indicates the orientation 5) → 3) of the locus, and the gene group order in the locus. The arrow is proportional to the size of the locus, indicated in kilobases (kb). The total number of genes in the locus is shown between parentheses. Depending on the haplotype, there are 7– 11 IGLC genes. In the 7-IGLC gene haplotype, each IGLC gene is preceded by one IGLJ gene in 5). Although the additional IGLC genes, in the 8-, 9-, 10- and 11-IGLC gene haplotypes have not yet been sequenced, they are probably preceded by one IGLJ gene. The number of functional genes defines the potential IGL repertoire, which comprises in the 7- IGLC gene haplotype, 37–43 genes (29–33 IGLV, 4–5 IGLJ and 4–5 IGLC) per haploid genome.
Source publication
'Nomenclature of the Human Immunoglobulin Lambda (IGL) Genes', the 18th report of the 'IMGT Locus in Focus' section, provides the first complete list of all the human IGL genes. The total number of human IGL genes per haploid genome is 87--96 (93--102 if the orphons are included), of which 37--43 genes are functional. IMGT/Human Genome Organization...
Context in source publication
Context 1
... IGL Locus at 22q11. 2 The human IGL locus is located at band 22q11.2 on the long arm of chromosome 22 [24,25] (fig. 1). The orientation of the locus has been determined by the analysis of trans- locations involving the IGL locus in leukemia and lymphoma. Sequencing of the long arm of chromosome 22 showed that it encompasses about 35 megabases of DNA and that the IGL locus is localized at 6 megabases from the cen- tromere ...
Citations
... The IGL region typically contains 7 to 11 highly similar J-C cassettes, ranging from 3.5-5.6 kb, each containing a J and a C gene segment (Lefranc 2001c). This IGL J-C cluster contains 9 cassettes, including one novel IGLC3 allele that differed from the closest known alleles by a single SNV (Supplemental Fig. S1). ...
Immunoglobulin (IGH, IGK, IGL) loci in the human genome are highly polymorphic regions that encode the building blocks of the light and heavy chain IG proteins that dimerize to form antibodies. The processes of V(D)J recombination and somatic hypermutation in B cells are responsible for creating an enormous reservoir of highly specific antibodies capable of binding a vast array of possible antigens. However, the antibody repertoire is fundamentally limited by the set of variable (V), diversity (D), and joining (J) alleles present in the germline IG loci. To better understand how the germline IG haplotypes contribute to the expressed antibody repertoire, we combined genome sequencing of the germline IG loci with single-cell transcriptome sequencing of B cells from the same donor. Sequencing and assembly of the germline IG loci captured the IGH locus in a single fully-phased contig where the maternal and paternal contributions to the germline V, D, and J repertoire can be fully resolved. The B cells were collected following a measles, mumps, and rubella (MMR) vaccination, resulting in a population of cells that were activated in response to this specific immune challenge. Single-cell, full-length transcriptome sequencing of these B cells resulted in whole transcriptome characterization of each cell, as well as highly-accurate consensus sequences for the somatically rearranged and hypermutated light and heavy chain IG transcripts. A subset of antibodies synthesized based on their consensus heavy and light chain transcript sequences demonstrated binding to measles antigens and neutralization of measles live virus.
... The 30 most abundant proteins in the amyloidoma region of cases 1 ( Figure 4A) included five immunoglobulin light chains (IGLV6-57, IGLC2, IGKV3-20, IGKC, IGKV2-40) and one heavy chain (IgG-1 heavy chain). The most abundant protein group, IGLV6-57 (Immunoglobulin lambda variable 6-57), is the variable domain of the λ6 light chain immunoglobulin [15]; its very high level indicates a local AL-lambda amyloidoma. IGLV6-57 was identified with 103 MS/MS spectra that matched to a single unique peptide, and which represents 17% sequence coverage. ...
The term amyloidoma applies to localized deposits of amyloid in the absence of systemic amyloidosis. Skeletal and soft tissue amyloidomas are very rare and the pathogenesis is usually associated with lymphoproliferative disorders or because of local chronic inflammation. Due to the rarity of the disease and the limited application of proteomics for diagnostic purposes, it is difficult to find datasets of mass spectrometry-based characterization of amyloidomas. Here we report the histological and immunohistochemical features of four cases of musculoskeletal amyloidoma in association with laser capture microdissection (LCM) and bottom-up microproteomics. Proteomics techniques allowed to elucidate the nature of the amyloid protein deposit, improving the results obtained by immunohistochemistry (IHC). IHC results were confirmed in two cases while laser-capture microdissection coupled with bottom-up microproteomics was necessary to type the other two cases, for which IHC was inconclusive.
... The human IGL locus consists of 73-74 IGLV genes [237,[269][270][271][272][273], localized on 900 kb, seven to 11 IGLJ and seven to 11 IGLC genes depending on the haplotypes, each IGLC gene being preceded by one IGLJ gene [274][275][276][277]. Fifty-six-57 genes belong to 11 subgroups, whereas 17 pseudogenes which are too divergent to be assigned to subgroups, have been assigned to the clans. The potential genomic IGL repertoire per haploid genome comprises 29-33 functional IGLV gnes in the 7-IGL gene haplotype [2,278,279]. One, two, three or four additional IGLC genes, each one probably preceded by one IGLJ, have been shown to characterize IGLC haplotypes with eight, nine, 10 or 11 genes [280,281], but these genes have not yet been sequenced. ...
IMGT®, the international ImMunoGeneTics® information system founded in 1989 by Marie-Paule Lefranc (Université de Montpellier and CNRS), marked the advent of immunoinformatics, a new science at the interface between immunogenetics and bioinformatics. For the first time, the immunoglobulin (IG) or antibody and T cell receptor (TR) genes were officially recognized as ‘genes’ as well as were conventional genes. This major breakthrough has allowed the entry, in genomic databases, of the IG and TR variable (V), diversity (D) and joining (J) genes and alleles of Homo sapiens and of other jawed vertebrate species, based on the CLASSIFICATION axiom. The second major breakthrough has been the IMGT unique numbering and the IMGT Collier de Perles for the V and constant (C) domains of the IG and TR and other proteins of the IG superfamily (IgSF), based on the NUMEROTATION axiom. IMGT-ONTOLOGY axioms and concepts bridge genes, sequences, structures and functions, between biological and computational spheres in the IMGT® system (Web resources, databases and tools). They provide the IMGT Scientific chart rules to identify, to describe and to analyse the IG complex molecular data, the huge diversity of repertoires, the genetic (alleles, allotypes, CNV) polymorphisms, the IG dual function (paratope/epitope, effector properties), the antibody humanization and engineering.
... : 'epppseetatioo du hhooosooe aaee looalisatioo du loous IGL, adaptt ddappps Lefranc et al. 28 : lncRNAs exprimés au cours de la différenciation B et dans les hémopathies lphoïdes B, adaptt ddappps Nooili et al. 110 . ......................................................................... 76 ...
... Le locus Immunoglobuline Lambda (ou IGL) est localisé sur le bras long du chromosome 22 en 22q11.2. Le locus fait environ 1050 kb 28 . LLooieetatioo du ggge IGL est sees, est-à-dire que la gioo est situue ôtt eettooooiiue et la paatie est looalisse au iieau ttlooooiiue ( Figure 14). ...
... LLooieetatioo du ggge IGL est sees, est-à-dire que la gioo est situue ôtt eettooooiiue et la paatie est looalisse au iieau ttlooooiiue ( Figure 14). Il contient 4 à 5 seggeets CC foootioooels pppppdds du seggeet JJ correspondant ( Figure 15) 3,28 . Les segments VV soot eggoupps ee 3 clusters différents contenant des eees de diffffeetes faailles de VV 3 . ...
La leucémie lymphoïde chronique (LLC) est le lymphome avec phase circulante le plus fréquent chez l’adulte dans les pays occidentaux. Elle est caractérisée par une grand hétérogénéité dans son évolution naturelle avec des formes indolentes ne nécessitant jamais de traitement spécifique et des formes agressives requérant une chimiothérapie rapidement après le diagnostic. Dans ce travail de thèse, nous avons posé la question du rôle des anomalies moléculaires et en particulier des gènes des immunoglobulines dans l’histoire naturelle de la maladie, tant au plan mécanistique que pour le pronostic. Nous avons étudié trois remaniements atypiques impliquant un gène des immunoglobulines et un partenaire inconnu dans la LLC/lymphome lymphocytique. Les points de cassure ont pu être identifiés et nous ont permis de mettre en évidence l’implication dans 2 cas d’ARN longs non codants en 17q25 et 8q24. De plus, deux cas ont des points de cassure dans une région chromosomique restreinte (espacés de 200 kb en 17q25). Il pourrait s’agir d’un locus important dans la lymphomagénèse, de même que pour la région 8q24 contenant MYC et de nombreux gènes non codants jusqu’ici peu explorés. Par ailleurs, dans l’ère du séquençage haut débit, de nombreux marqueurs pronostiques moléculaires sont décrits dans la LLC. Nous avons démontré que l’électrophorèse des protéines sériques normale (immunoglobulines polyclonales sans hypogammaglobulinémie) au diagnostic, un marqueur simple et peu couteux, reste dans l’ère du NGS, un marqueur indépendant de bon pronostic dans la LLC. Sa combinaison avec un statut IGHV muté identifie un groupe de patients qui n’auront probablement jamais besoin de traitement spécifique. Ce travail nous a conduit à mettre au point un outil performant de détection des anomalies de nombre de copies par séquençage haut débit. Celui-ci permet la mise en évidence de disomies uniparentales dont la signification pronostique n’est actuellement pas établie dans la LLC. Ces anomalies pourraient être le reflet d’une instabilité chromosomique et il serait intéressant d’étudier leur impact pronostique dans la LLC.
... Here we seek the molecular basis of the formation of amyloid fibrils from Ig light chains of both lambda and kappa families. The Human Gene Nomenclature Committee lists 33 functional genes for lambda and 38 for kappa variable domains (27)(28)(29). The repertoire of VLs is greatly expanded by the linkage of lambda and kappa domains to a variety of J-segments and constant domains. ...
Systemic light chain amyloidosis (AL) is a human disease caused by overexpression of monoclonal immunoglobulin light chains that form pathogenic amyloid fibrils. These amyloid fibrils deposit in tissues and cause organ failure. Proteins form amyloid fibrils when they partly or fully unfold and expose segments capable of stacking into β-sheets that pair and thereby form a tight, dehydrated interface. These structures, termed steric zippers, constitute the spines of amyloid fibrils. Here, using a combination of computational (with ZipperDB and Boston University ALBase), mutational, biochemical, and protein structural analyses, we identified segments within the variable domains of Ig light chains that drive the assembly of amyloid fibrils in AL. We demonstrate that there are at least two such segments and that each one can drive amyloid fibril assembly independently of the other. Our analysis revealed that peptides derived from these segments form steric zippers featuring a typical dry interface with high-surface complementarity and occupy the same spatial location of the Greek-key immunoglobulin fold in both lambda and kappa variable domains. Of note, some predicted stericzipper segments did not form amyloid fibrils or assembled into fibrils only when removed from the whole protein. We conclude that steric zipper propensity must be by experimentally validated and that the two segments identified here may represent therapeutic targets. In addition to elucidating the molecular pathogenesis of AL, these findings also provide an experimental approach for identifying segments that drive fibril formation in other amyloid diseases.
... Additionally, in mice the prevalence of serum immunoglobulin utilizing a lambda light chain is severely reduced relative to immunoglobulin utilizing a kappa light chain [36]. By contrast, the human Ig locus is more complex and encodes greater than 35 V genes belonging to 10 subgroups [37]. Moreover, the distribution of kappa and lambda immunoglobulin is more balanced in human serum [38]. ...
The domestic ferret ( Mustela putorius furo ) serves as an animal model for the study of several viruses that cause human disease, most notably influenza. Despite the importance of this animal model, characterization of the immune response by flow cytometry (FCM) is severely hampered due to the limited number of commercially available reagents. To begin to address this unmet need and to facilitate more in-depth study of ferret B cells including the identification of antibody-secreting cells, eight unique murine monoclonal antibodies (mAb) with specificity for ferret immunoglobulin (Ig) were generated using conventional B cell hybridoma technology. These mAb were screened for reactivity against ferret peripheral blood mononuclear cells by FCM and demonstrate specificity for CD79 β⁺ B cells. Several of these mAb are specific for the light chain of surface B cell receptor (BCR) and enable segregation of kappa and lambda B cells. Additionally, a mAb that yielded surface staining of nearly all surface BCR positive cells ( i.e. , pan ferret Ig) was generated. Collectively, these M α F-Ig mAb offer advancement compared to the existing portfolio of polyclonal anti-ferret Ig detection reagents and should be applicable to a wide array of immunologic assays including the identification of antibody-secreting cells by FCM.
... Additionally, in mice the prevalence of serum immunoglobulin utilizing a lambda light chain is severely reduced relative to immunoglobulin utilizing a kappa light chain [36]. By contrast, the human Ig locus is more complex and encodes greater than 35 V genes belonging to 10 subgroups [37]. Moreover, the distribution of kappa and lambda immunoglobulin is more balanced in human serum [38]. ...
The supplementary material offers data supporting the lack of heavy chain specificity observed using commercially available anti-ferret immunoglobulin antiserum. Additionally, the mouse immunization scheme and characterization of the polyclonal serum antibody response against the ferret Ig antigen are detailed.
... Human κ and λ chain loci are located at 2p11.2 and 22q11.2, respectively, and comprise 40 and 30 Vκ and Vλ segments, respectively, and 5 Jκ and 4 Jλ, respectively and one CL segment each (11,12). ...
Gedächtnis-B-Zellen und Plasmazellen sind essentielle Komponenten der protektiven Immunität. Die Mechanismen ihrer Induktion, ihres Überlebens und der Gedächtnis-B-Zellreaktivierung sind allerding bisher nur unvollständig verstanden. Um unser Wissen diesbezüglich zu erweitern, wurden in der vorliegenden Arbeit zum einen Charakteristika von Primär- und Sekundärimmunantworten nach Immunisierung mit Keyhole Limpet Hemocyanin (KLH) untersucht und zum anderen das Vorkommen sowie der Phänotyp humaner Gedächtnis-B-Zellen in verschiedenen lymphatischen Geweben analysiert. Die primäre parenterale KLH Immunisierung führte auf serologischer und zellulärer Ebene zu einer Reihe unerwarteter Ergebnisse, welche u. a. das Auftreten von IgA Antikörpern und die gleichzeitige Präsenz von hoch- und wenig mutierten primären Plasmablasten beinhalteten. Die Untersuchung der Gedächtnis-B-Zellverteilung in verschiedenen lymphatischen Geweben ergab den größten Gedächtnis-B-Zellpool in der Milz. Blut-, Tonsillen-, Knochenmarks- und Milz-Gedächtnis-B-Zellen wiesen nur wenige phänotypische Unterschiede auf. Einer davon war die CD69 Expression auf tonsillären ruhenden Gedächtnis-B-Zellen, was darauf hindeutet, dass tonsilläre Gedächtnis-B-Zellen tatsächlich sessil sein könnten. Die hier erhaltenen Ergebnisse stellen neue Erkenntnisse über bisher unbeschriebene Mechanismen bei parenteralen Immunantworten wie zum Beispiel die Induktion von IgA Antikörpern sowie die potentielle Rekrutierung kreuzreaktiver Gedächtnis-B-Zellen dar. Es bleibt zu klären, wie die Reaktivierung solcher Gedächtnis-B-Zellen reguliert ist. Derartiges Wissen wäre insbesondere für Therapien von Erkrankungen des Immunsystems, wie Autoimmunität, von Bedeutung. Das potentiell patrouillierende Verhalten der Gedächtnis-B-Zellen ist ein markanter Unterschied zu den nischenabhängigen sessilen Plasmazellen und deutet weitestgehend darauf hin, dass Gedächtnis-B-Zellen nicht auf derartige Nischen angewiesen sind.
... In silico analyses identified the heavy chain locus on two unplaced contigs, which are called Un0011 and Un0038 ( Fig. 1a and b, Tables 1e3). The nomenclature used in previous studies to denominate Ig heavy and light chain gene segments varied, although they conformed to current definitions by the international ImMunoGeneTics (IMGT) information system, as well as to the WHOeIUIS Nomenclature Subcommittee for immunoglobulins and T-cell receptors ( Hara et al., 2012;Lefranc, 2001bLefranc, , 2007Sun et al., 2010;Tallmadge et al., 2014Tallmadge et al., , 2013). Nevertheless, in the designation system ( Tallmadge et al., 2014) used most recently, pseudogenes and open reading frames are not indicated precisely. ...
Our understanding of how equine immunoglobulin genes are organized has increased significantly in recent years. For equine heavy chains, 52 IGHV, 40 IGHD, 8 IGHJ and 11 IGHC are present. Seven of these IGHCs are gamma chain genes. Sequence diversity is increasing between fetal, neonatal, foal and adult age. The kappa light chain contains 60 IGKV, 5 IGKJ and 1 IGKC, whereas there are 144 IGLV, 7 IGLJ, and 7 IGLC for the lambda light chain, which is expressed predominantly in horses. Significant transcriptional differences for IGLV and IGLC are identified in different breeds. Allotypic and allelic variants are observed for IGLC1, IGLC5, and IGLC6/7, and two IGLV pseudogenes are also transcribed. During age development, a decrease in IGLVs is noted, although nucleotide diversity and significant differences in gene usage increased. The following paper suggests a standardization of the existing nomenclature of immunoglobulin genes.
Copyright © 2015. Published by Elsevier Ltd.
... The human IGK light chain locus comprises 76 V K gene segments, grouped into 7 families, 5 J j , and one C j gene segments. The IGL locus contains 70-71 functional and pseudo V L gene segments, grouped into 10 families and organized in three large separate clusters, as well as seven J L -C L regions, of which only J L1 -C L1 , J L2 -C L2 , J L3 -C L3, and J L7 -C L7 regions are functional (Lefranc, 2001;Gonz alez et al., 2007). ...
Multiple myeloma (MM) is a malignant B-cell neoplasm characterized by an uncontrolled proliferation of aberrant plasma cells in the bone marrow. Chromosome aberrations in MM are complex and represent a hallmark of the disease, involving many chromosomes that are altered both numerically and structurally. Nearly half of the cases are nonhyperdiploid and show IGH translocations with the following partner genes: CCND1, FGFR3 and MMSET, MAF, MAFB, and CCND3. The remaining 50% are grouped into a hyperdiploid group that is characterized by multiple trisomies involving chromosomes 3, 5, 7, 9, 11, 15, 19, and 21. In this study, we analyzed the immunoglobulin light chain kappa (IGK, 2p12) and lambda (IGL, 22q11) loci in 150 cases, mostly with MM but in a few cases monoclonal gammopathy of undetermined significance (MGUS), without IGH translocations. We identified aberrations in 27% (= 40 patients) including rearrangements (12%), gains (12%), and deletions (4.6%). In 6 of 18 patients with IGK or/and IGL rearrangements, we detected a MYC rearrangement which suggests that MYC is the translocation partner in the majority of these cases. © 2014 Wiley Periodicals, Inc.
