المؤلفون: Zaixin Liu, Xueqing Ma, Yuanfang Fu, Yimei Cao, Shasha Zhou, Yingli Chen, Guoqiang Zhu, Huifang Bao, Hengmei Wang, Dong Li, Zengjun Lu, Jing Zhang, Pu Sun, Pinghua Li, Xingwen Bai, Kun Li

المصدر: Journal of General Virology. 102

مصطلحات موضوعية: 0301 basic medicine, Swine, medicine.drug_class, Genes, Immunoglobulin Heavy Chain, viruses, 030106 microbiology, Antibody Affinity, Antibodies, Viral, Serogroup, Immunoglobulin light chain, Monoclonal antibody, Epitope, Epitopes, 03 medical and health sciences, Antigen, Virology, medicine, Animals, Antigens, Viral, B-Lymphocytes, Linear epitope, biology, Antibodies, Monoclonal, virus diseases, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, 030104 developmental biology, Foot-and-Mouth Disease Virus, Immunoglobulin G, biology.protein, Capsid Proteins, Immunoglobulin Light Chains, Genes, Immunoglobulin Light Chain, Foot-and-mouth disease virus, Antibody, Immunoglobulin Heavy Chains, Epitope Mapping, Conformational epitope

الوصف: Pigs are susceptible to foot-and-mouth disease virus (FMDV), and the humoral immune response plays an essential role in protection against FMDV infection. However, little information is available about FMDV-specific mAbs derived from single B cells of pigs. This study aimed to determine the antigenic features of FMDV that are recognized by antibodies from pigs. Therefore, a panel of pig-derived mAbs against FMDV were developed using fluorescence-based single B cell antibody technology. Western blotting revealed that three of the antibodies (1C6, P2-7E and P2-8G) recognized conserved antigen epitopes on capsid protein VP2, and exhibited broad reactivity against both FMDV serotypes A and O. An alanine-substitution scanning assay and sequence conservation analysis elucidated that these porcine mAbs recognized two conserved epitopes on VP2: a linear epitope (2KKTEETTLL10) in the N terminus and a conformational epitope involving residues K63, H65, L66, F67, D68 and L81 on two β-sheets (B-sheet and C-sheet) that depended on the integrity of VP2. Random parings of heavy and light chains of the IgGs confirmed that the heavy chain is predominantly involved in binding to antigen. The light chain of porcine IgG contributes to the binding affinity toward an antigen and may function as a support platform for antibody stability. In summary, this study is the first to reveal the conserved antigenic profile of FMDV recognized by porcine B cells and provides a novel method for analysing the antibody response against FMDV in its natural hosts (i.e. pigs) at the clonal level.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aaa6f1ee3e4a63b3625ea322a67f702bTest
https://doi.org/10.1099/jgv.0.001608Test

المؤلفون: Or Shemesh, Pazit Polak, Knut E. A. Lundin, Ludvig M. Sollid, Gur Yaari

المصدر: Frontiers in Immunology
Frontiers in Immunology, Vol 12 (2021)

مصطلحات موضوعية: lcsh:Immunologic diseases. Allergy, Tissue transglutaminase, Genes, Immunoglobulin Heavy Chain, Immunology, Naive B cell, Receptors, Antigen, B-Cell, Human leukocyte antigen, Adaptive Immunity, Immunoglobulin light chain, immune response, Epitope, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, Immune system, Databases, Genetic, Cluster Analysis, Data Mining, Humans, Immunology and Allergy, Original Research, 030304 developmental biology, B-Lymphocytes, 0303 health sciences, biology, breakpoint cluster region, naïve B-cells, 3. Good health, Celiac Disease, Case-Control Studies, biology.protein, Genes, Immunoglobulin Light Chain, BCR repertoire, Antibody, lcsh:RC581-607, 030215 immunology

الوصف: Celiac disease (CeD) is a common autoimmune disorder caused by an abnormal immune response to dietary gluten proteins. The disease has high heritability. HLA is the major susceptibility factor, and the HLA effect is mediated via presentation of deamidated gluten peptides by disease-associated HLA-DQ variants to CD4+ T cells. In addition to gluten-specific CD4+ T cells the patients have antibodies to transglutaminase 2 (autoantigen) and deamidated gluten peptides. These disease-specific antibodies recognize defined epitopes and they display common usage of specific heavy and light chains across patients. Interactions between T cells and B cells are likely central in the pathogenesis, but how the repertoires of naïve T and B cells relate to the pathogenic effector cells is unexplored. To this end, we applied machine learning classification models to naïve B cell receptor (BCR) repertoires from CeD patients and healthy controls. Strikingly, we obtained a promising classification performance with an F1 score of 85%. Clusters of heavy and light chain sequences were inferred and used as features for the model, and signatures associated with the disease were then characterized. These signatures included amino acid (AA) 3-mers with distinct bio-physiochemical characteristics and enriched V and J genes. We found that CeD-associated clusters can be identified and that common motifs can be characterized from naïve BCR repertoires. The results may indicate a genetic influence by BCR encoding genes in CeD. Analysis of naïve BCRs as presented here may become an important part of assessing the risk of individuals to develop CeD. Our model demonstrates the potential of using BCR repertoires and in particular, naïve BCR repertoires, as disease susceptibility markers.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ed601ea0f57508d7e7a4ca9f778fc915Test
https://doi.org/10.3389/fimmu.2021.627813Test

المؤلفون: Tian Huang, Gengsheng Cao, Zheya Sheng, Xiaoxing Guan, Linyun Guo

المصدر: Developmental & Comparative Immunology. 89:66-72

مصطلحات موضوعية: 0301 basic medicine, Immunology, Gene Expression, Locus (genetics), Biology, Genome, Avian Proteins, Evolution, Molecular, 03 medical and health sciences, Phylogenetics, Gene Duplication, Sequence Homology, Nucleic Acid, Gene duplication, Animals, Columbidae, Gene, Phylogeny, Genomic organization, Base Sequence, Phylogenetic tree, Genetic Variation, biology.organism_classification, V(D)J Recombination, 030104 developmental biology, Evolutionary biology, Immunoglobulin Light Chains, Genes, Immunoglobulin Light Chain, Neoaves, Developmental Biology

الوصف: Previous studies on immunoglobulin light chain (IgL) genes in avian species are limited to Galloanseres, and few studies have investigated IgL genes in Neoaves, which includes most living birds. Based on published genome data, we demonstrate that the pigeon ( Columba livia ) IgL locus spans approximately 24 kb of DNA and contains twenty Vλ segments located upstream of a single pair of Jλ-Cλ. Among the identified Vλ gene segments, four segments are structurally intact and all four segments are able to recombine with Jλ. Moreover, the four functional Vλ segments are preferentially utilized in VλJλ recombination. Phylogenetic analysis suggests that the presence of the four functional Vλ segments in pigeon was likely generated by gene duplication that occurred after the divergence of pigeon and other birds. Our study provides insight into IgL gene evolution and evolutionary diversity of Ig genes in birds.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7d0218d1fe8a45ae92cdb6122e52d35aTest
https://doi.org/10.1016/j.dci.2018.08.006Test

المؤلفون: Bryan Briney, Dennis R. Burton, Collin Joyce

المصدر: Scientific Reports
Scientific Reports, Vol 10, Iss 1, Pp 1-9 (2020)

مصطلحات موضوعية: 0301 basic medicine, Genes, Immunoglobulin Heavy Chain, lcsh:Medicine, Datasets as Topic, Somatic hypermutation, Computational biology, Biology, Immunoglobulin light chain, Article, DNA sequencing, 03 medical and health sciences, Immunoglobulin kappa-Chains, 0302 clinical medicine, Species Specificity, Antibody Repertoire, Immunogenetics, Animals, Humans, lcsh:Science, Data mining, Gene, Multidisciplinary, Sequence Homology, Amino Acid, Repertoire, lcsh:R, Genetic Variation, High-Throughput Nucleotide Sequencing, Antibody Diversity, Immunoglobulin Class Switching, V(D)J Recombination, Rats, 030104 developmental biology, Immunoglobulin class switching, Organ Specificity, biology.protein, lcsh:Q, VDJ Exons, Genes, Immunoglobulin Light Chain, Lymph Nodes, Somatic Hypermutation, Immunoglobulin, Rats, Transgenic, Antibody, Sequence Alignment, Software, Spleen, 030215 immunology

الوصف: The humanization of animal model immune systems by genetic engineering has shown great promise for antibody discovery, tolerance studies and for the evaluation of vaccines. Assessment of the baseline antibody repertoires of unimmunized model animals will be useful as a benchmark for future immunization experiments. We characterized the heavy chain and kappa light chain antibody repertoires of a model animal, the OmniRat, by high throughput antibody sequencing and made use of two novel datasets for comparison to human repertoires. Intra-animal and inter-animal repertoire comparisons reveal a high level of conservation in antibody diversity between the lymph node and spleen and between members of the species. Multiple differences were found in both the heavy and kappa chain repertoires between OmniRats and humans including gene segment usage, CDR3 length distributions, class switch recombination, somatic hypermutation levels and in features of V(D)J recombination. The Inference and Generation of Repertoires (IGoR) software tool was used to model recombination in VH regions which allowed for the quantification of some of these differences. Diversity estimates of the OmniRat heavy chain repertoires almost reached that of humans, around two orders of magnitude less. Despite variation between the species repertoires, a high frequency of OmniRat clonotypes were also found in the human repertoire. These data give insights into the development and selection of humanized animal antibodies and provide actionable information for use in vaccine studies.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::131a387d2607f885dc1e7ff325c2e370Test
https://doi.org/10.1101/776385Test

المؤلفون: Chun-Chi Kuo, Ying-Zhen Su, Meng-Chen Tsai, Yen-Chuan Hsieh, Shih-Sung Chuang

المصدر: Diagnostic Cytopathology. 46:685-689

مصطلحات موضوعية: Male, Pathology, medicine.medical_specialty, Histology, Pleural effusion, Hepatitis C virus, medicine.disease_cause, Virus, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Immunophenotyping, Lymphoma, Primary Effusion, medicine, Gene Rearrangement, B-Lymphocyte, Light Chain, Humans, Lymphocytes, Aged, 80 and over, medicine.diagnostic_test, business.industry, General Medicine, Gene rearrangement, medicine.disease, Lymphoma, Effusion, 030220 oncology & carcinogenesis, Genes, Immunoglobulin Light Chain, business, 030215 immunology, Fluorescence in situ hybridization

الوصف: Effusion-based lymphoma (EBL) is a rare but distinct entity of large B-cell lymphoma in effusion without association with human herpes virus-8 (HHV-8). Spontaneous regression after pleurocentesis has been observed; but to our knowledge, there are no reports on the morphological and molecular features of subsequent aspirations in regressing cases. Here, we report the case of a 92-year-old male with chronic obstructive pulmonary disease, who presented with right pleural effusion. He had no human immunodeficiency virus, hepatitis B virus, or hepatitis C virus infection, and CT scans revealed no mass lesion. The first pleural effusion aspiration cytology revealed large lymphoma cells with vesicular nuclei, irregular nuclear contours, and prominent nucleoli, consistent with EBL. The second aspiration cytology showed a few slightly enlarged lymphocytes in a background of small lymphocytes. Immunohistochemical study on cell block of the second aspiration revealed equal amounts of CD3-positive and CD20-positive cells. All these cells on the section tested negative for HHV-8 through immunohistochemistry and Epstein-Barr virus by in situ hybridization. Our initial impression was EBL in regression. However, flow cytometric immunophenotyping showed monotypic light chain expression of the gated B-cells. B-cell receptor gene rearrangement study showed a clonal result. Furthermore, fluorescence in situ hybridization revealed rearrangement of IGH gene. The diagnosis of the second aspiration was EBL with morphological regression but retained clonal genetic features. The patient passed away one month after diagnosis without chemotherapy. This case illustrated the importance of ancillary studies in confirming the clonal nature of a morphologically regressing EBL.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8df66608cfd22c426b90eca0bd52db40Test
https://doi.org/10.1002/dc.23922Test

المؤلفون: Jiri Jarkovsky, Roman Hájek, Tereza Sevcikova, Katerina Growkova, Lucie Brozova, Jana Filipova, Elena Kryukova, Zuzana Kufova, Fedor Kryukov

المصدر: Gene. 591:490-498

مصطلحات موضوعية: 0301 basic medicine, Genetics, Gene Expression Profiling, Paraproteinemias, Plasma cell dyscrasia, Amyloidosis, General Medicine, Biology, medicine.disease, Ribosome, 3. Good health, Immunoglobulin Light-chain Amyloidosis, Gene expression profiling, 03 medical and health sciences, 030104 developmental biology, Ribosomal protein, medicine, AL amyloidosis, Animals, Humans, Genes, Immunoglobulin Light Chain, Gene, Monoclonal gammopathy of undetermined significance

الوصف: Immunoglobulin light chain amyloidosis (ALA) is a plasma cell dyscrasia characterized by deposition of amyloid fibrils in various organs and tissues. The current paper is devoted to clarify if ALA has a unique gene expression profile and to its pathogenetic argumentation. The meta-analysis of ALA patients vs. healthy donors, monoclonal gammopathy of undetermined significance, smoldering and multiple myeloma patients' cohorts have revealed molecular signature of ALA consists of 256 genes representing mostly ribosomal proteins and immunoglobulin regions. This signature appears pathogenetically supported and elucidates for the first time the role of ribosome dysfunction in ALA. In summary of our findings with literature overview, we hypothesize that ALA development is associated not only with changes in genes, coding amyloidogenic protein itself, but with post-transcriptional disbalance as well. Based on our data analysis in ALA, ribosome machinery is impaired and the affected link mainly involves translational initiation, elongation and co-translational protein folding.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d42034f366af043b3bfb9f34f4bc560Test
https://doi.org/10.1016/j.gene.2016.06.017Test

المؤلفون: Olivier Giger, Anthony J. Bench, Ming-Qing Du, Lívia Rásó-Barnett, Yuanxue Huang, Michael A. Scott, Anna L. Paterson, Hesham Eldaly, Thomas Roberts, Hani Bibawi, Hongxiang Liu, Baljinder K Matharu, Elizabeth J. Soilleux

المصدر: British journal of haematology. 185(2)

مصطلحات موضوعية: Lymphoma, B-Cell, Immunoglobulin lambda light chain gene, Biology, Polymerase Chain Reaction, Clonal Immunoglobulin Gene Rearrangement, 03 medical and health sciences, Immunoglobulin kappa-Chains, 0302 clinical medicine, Immunoglobulin lambda-Chains, medicine, Gene Rearrangement, B-Lymphocyte, Light Chain, Humans, Gene, B cell, Aged, Clonality Analysis, Hematology, Molecular biology, B-cell neoplasm, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Female, Genes, Immunoglobulin Light Chain, Neoplasm Grading, Immunoglobulin Heavy Chains, 030215 immunology, Genes, Neoplasm

الوصف: Identification of clonal IGH, IGK and IGL gene rearrangements offers diagnostic adjunct in suspected B-cell neoplasms. However, many centres omit IGL analysis as its value is uncertain. A review of 567 cases with IGH, IGK and IGL rearrangement assessed using BIOMED-2 assays showed clonal immunoglobulin gene rearrangement in 54% of cases, of which 24% had a clonal IGL rearrangement. In two cases, the clonal rearrangement was detected exclusively by IGL analysis. This finding demonstrates the added value of IGL analysis for clonality assessment, especially in suspected B-cell neoplasms in which a clonal IGH and/or IGK rearrangement is not detected or is equivocal.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::685292d05cc2d5211efe082b35e4a01bTest
https://pubmed.ncbi.nlm.nih.gov/30681735Test

المؤلفون: Andrew M. Collins, Corey T. Watson

المصدر: Frontiers in Immunology
Frontiers in Immunology, Vol 9 (2018)

مصطلحات موضوعية: lcsh:Immunologic diseases. Allergy, 0301 basic medicine, Immunology, Mice, Inbred Strains, Review, Biology, Immunoglobulin light chain, Germline, Antibodies, 03 medical and health sciences, Antibody Repertoire, Species Specificity, antibody repertoire, Immunology and Allergy, Animals, Receptors, Immunologic, Gene, Genomic organization, immunoglobulin light chain, Genetics, Gene Rearrangement, sub-species of the house mouse, Repertoire, models of autoimmune disease, receptor editing, self-tolerance, Receptor editing, Genetic Variation, 030104 developmental biology, V(D)J rearrangement, Self Tolerance, Immunoglobulin Light Chains, Genes, Immunoglobulin Light Chain, lcsh:RC581-607, Function (biology)

الوصف: Discussion of the antibody repertoire usually emphasizes diversity, but a conspicuous feature of the light chain repertoire is its lack of diversity. The diversity of reported allelic variants of germline light chain genes is also limited, even in well-studied species. In this review, the implications of this lack of diversity are considered. We explore germline and rearranged light chain genes in a variety of species, with a particular focus on human and mouse genes. The importance of the number, organization and orientation of the genes for the control of repertoire development is discussed, and we consider how primary rearrangements and receptor editing together shape the expressed light chain repertoire. The resulting repertoire is dominated by just a handful of IGKV and IGLV genes. It has been hypothesized that an important function of the light chain is to guard against self-reactivity, and the role of secondary rearrangements in this process could explain the genomic organization of the light chain genes. It could also explain why the light chain repertoire is so limited. Heavy and light chain genes may have co-evolved to ensure that suitable light chain partners are usually available for each heavy chain that forms early in B cell development. We suggest that the co-evolved loci of the house mouse often became separated during the inbreeding of laboratory mice, resulting in new pairings of loci that are derived from different sub-species of the house mouse. A resulting vulnerability to self-reactivity could explain at least some mouse models of autoimmune disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::69a5205008b4403dcfd6cba6a74d575cTest
http://europepmc.org/articles/PMC6186787Test

المؤلفون: Huabin Zhu, Haisheng Hao, Tong Qin, Dong Wang, Weihua Du, Huijing Zhao

المصدر: Immunology Letters. 166:79-86

مصطلحات موضوعية: Genes, Immunoglobulin Heavy Chain, Pseudogene, Molecular Sequence Data, Immunology, Locus (genetics), Biology, Animals, Immunology and Allergy, Gene family, Amino Acid Sequence, Gene, Phylogeny, Genomic organization, Genetics, Base Sequence, Genes, Immunoglobulin, Arvicolinae, Chromosome Mapping, Antibody Diversity, Genomics, biology.organism_classification, Prairie vole, Genetic Loci, Multigene Family, Immunoglobulin heavy chain, Genes, Immunoglobulin Light Chain, Sequence Alignment

الوصف: In science, the prairie voles are ideal models for studying the regulatory mechanisms of social behavior in humans. The utility of the prairie vole as a biology model can be further enhanced by characterization of the genes encoding components of the immune system. Here, we report the genomic organization of the prairie vole immunoglobulin heavy and light chain genes. The prairie vole IgH locus on chromosome 1 spans over 1600 kb, and consists of at least 79 V H segments (28 potentially functional genes, 2 ORFs and 49 pseudogenes), 7 D H segments, 4 J H segments, four constant region genes (μ, γ, ɛ, and α), and two transmembrane regions of δ gene. The Igκ locus, found on three scaffolds (JH996430, JH996605 and JH996566), contains a totle of 124 V κ segments (47 potentially functional genes, 1 ORF and 76 pseudogenes), 5 J κ segments and a single C κ gene. Two different transcriptional orientations were determined for these V κ gene segments. In contrast, the Igλ locus on scaffold JH996473 and JH996489 includes 21 V λ gene segments (14 potentially functional genes, 1 ORF and 6 pseudogenes), all with the same transcriptional polarity as the downstream J λ -C λ cluster. Phylogenetic analysis and sequence alignments suggested the prairie vole's large germline V H , V κ and V λ gene segments appear to form limited gene families. Therefore, this species may generate antibody diversity via a gene conversion-like mechanism associated with its pseudogene reserves.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::418b134e19861870528e880965599a08Test
https://doi.org/10.1016/j.imlet.2015.06.001Test

المؤلفون: Lijuan Du, Jie Wu, Mingli Wu, Xiaohui Yu, Shuai He, Tingting Yuan, Xiuzhu Sun

المصدر: Immunobiology. 225:151889

مصطلحات موضوعية: 0301 basic medicine, Genetics, Goats, Pseudogene, Immunology, Immunoglobulin Variable Region, Somatic hypermutation, Locus (genetics), Hematology, Biology, Immunoglobulin light chain, Genome, Immunoglobulin kappa-Chains, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Animals, Immunology and Allergy, Genes, Immunoglobulin Light Chain, ORFS, Gene, Phylogeny, 030215 immunology, Genomic organization

الوصف: The genomic organization of goat immunoglobulin light chains (Igλ and Igκ) loci were annotated based on the goat genome database. The goat Igλ chain located on chromosome 17 contains at least 35 Vλ gene fragments (seven potential functional genes, one ORF and 27 pseudogenes), two Jλ-Cλ clusters arranged in a Vλ(35)-Jλ2-Cλ1-Jλ1-Cλ2 pattern, with another Cλ3 on scaffold. The Igκ locus included 11 Vκ (five potential functional genes, two ORFs and four pseudogene fragments), three Jκ genes and a single Cκ gene ordered in Vκ(35)-Jκ(3)-Cκ pattern on chromosome 11. By analyzing the clonies of Igλ and Igκ, we further found Vλ2 (26.23 %) &Vλ3 (73.11 %), Vκ2 (52.07 %) &Vκ4 (46.15 %) were predominately used in the expression of λ and κ chains respectively. λ chain showed more abundance in connective diversity than κ chain. Besides, somatic hypermutation with higher frequency in both immunoglobulin light chains was the major mechanism for the goat repertoire diversity. These results demonstrated goat immunoglobulin light chain variable region genome loci and repertoire diversity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5c941891f79a47cfcbc18b21bc06d6aTest
https://doi.org/10.1016/j.imbio.2019.11.024Test