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VDJ Recombination

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https://www.readbyqxmd.com/read/29568935/integrated-analysis-of-b%C3%A2-cell-and-t%C3%A2-cell-receptors-by-high%C3%A2-throughput-sequencing-reveals-conserved-repertoires-in-iga-nephropathy
#1
Minglin Ou, Fengping Zheng, Xinzhou Zhang, Song Liu, Donge Tang, Peng Zhu, Jingjun Qiu, Yong Dai
Immunoglobulin A nephropathy (IgAN) is a type of glomerular disorder associated with immune dysregulation, and understanding B‑/T‑cell receptors (BCRs/TCRs) may be valuable for the development of specific immunotherapeutic interventions. In the present study, B and T cells were isolated from IgAN patients and healthy controls, and the composition of the BCR/TCR complementarity‑determining region (CDR)3 was analyzed by multiplex polymerase chain reaction, high‑throughput sequencing and bioinformatics...
March 20, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29515575/high-throughput-sequencing-of-the-expressed-torafugu-takifugu-rubripes-antibody-sequences-distinguishes-igm-and-igt-repertoires-and-reveals-evidence-of-convergent-evolution
#2
Xi Fu, Jianqiang Sun, Engkong Tan, Kentaro Shimizu, Md Shaheed Reza, Shugo Watabe, Shuichi Asakawa
B-cell antigen receptor (BCR) or antibody diversity arises from somatic recombination of immunoglobulin (Ig) gene segments and is concentrated within the Ig heavy (H) chain complementarity-determining region 3 (CDR-H3). We performed high-throughput sequencing of the expressed antibody heavy-chain repertoire from adult torafugu. We found that torafugu use between 70 and 82% of all possible V (variable), D (diversity), and J (joining) gene segment combinations and that they share a similar frequency distribution of these VDJ combinations...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29508024/t-cell-receptor-%C3%AE-v-and-j-usage-in-combination-with-particular-hla-class-i-and-class-ii-alleles-correlates-with-cancer-survival-patterns
#3
Blake M Callahan, John M Yavorski, Yaping N Tu, Wei Lue Tong, Jacob C Kinskey, Kendall R Clark, Timothy J Fawcett, George Blanck
Class I and class II HLA proteins, respectively, have been associated with subsets of V(D)J usage resulting from recombination of the T-cell receptor (TCR) genes. Additionally, particular HLA alleles, in combination with dominant TCR V(D)J recombinations, have been associated with several autoimmune diseases. The recovery of TCR recombination reads from tumor specimen exome files has allowed rapid and extensive assessments of V(D)J usage, likely for cancer resident T-cells, across relatively large cancer datasets...
March 5, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29459861/in-depth-analysis-of-human-neonatal-and-adult-igm-antibody-repertoires
#4
Binbin Hong, Yanling Wu, Wei Li, Xun Wang, Yumei Wen, Shibo Jiang, Dimiter S Dimitrov, Tianlei Ying
Although high-throughput sequencing and associated bioinformatics technologies have enabled the in-depth, sequence-based characterization of human immune repertoires, only a few studies on a relatively small number of sequences explored the characteristics of antibody repertoires in neonates, with contradictory conclusions. To gain a more comprehensive understanding of the human IgM antibody repertoire, we performed Illumina sequencing and IMGT/HighV-QUEST analysis of IgM heavy chain repertoire of the B lymphocytes from the cord blood (CB) of neonates, as well as the repertoire from peripheral blood of healthy human adults (HH)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29204143/local-chromatin-features-including-pu-1-and-ikaros-binding-and-h3k4-methylation-shape-the-repertoire-of-immunoglobulin-kappa-genes-chosen-for-v-d-j-recombination
#5
Louise S Matheson, Daniel J Bolland, Peter Chovanec, Felix Krueger, Simon Andrews, Hashem Koohy, Anne E Corcoran
V(D)J recombination is essential for the generation of diverse antigen receptor (AgR) repertoires. In B cells, immunoglobulin kappa ( Igκ ) light chain recombination follows immunoglobulin heavy chain ( Igh ) recombination. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed that two chromatin states at the recombination signal sequence (RSS) of VH genes are highly predictive of recombination in mouse pro-B cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29038163/bcl11a-is-a-critical-component-of-a-transcriptional-network-that-activates-rag-expression-and-vdj-recombination
#6
Baeck-Seung Lee, Bum-Kyu Lee, Vishwanath R Iyer, Barry P Sleckman, Arthur L Shaffer, Gregory C Ippolito, Haley O Tucker, Joseph D Dekker
Recombination activating gene 1 (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining (VDJ) segment recombination, an essential process for antigen receptor expression and lymphocyte development. The BCL11A transcription factor is required for B cell and Plasmacytoid dendritic cell (pDC) development, but its molecular function(s) in early B cell fate specification and commitment are unknown. We show here that the major B cell isoform, BCL11A-XL, binds directly to the RAG1 promoter as well as directly to regulatory regions of transcription factors previously implicated in both B cell and pDC development to activate RAG1 and RAG2 transcription in pro- and pre-B cells...
October 16, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28916186/clinical-immunologic-and-genetic-spectrum-of-696-patients-with-combined-immunodeficiency
#7
Hassan Abolhassani, Janet Chou, Wayne Bainter, Craig D Platt, Mahmood Tavassoli, Tooba Momen, Marzieh Tavakol, Mohammad Hossein Eslamian, Mohammad Gharagozlou, Masoud Movahedi, Mohsen Ghadami, Amir Ali Hamidieh, Gholamreza Azizi, Reza Yazdani, Mohsen Afarideh, Alireza Ghajar, Arash Havaei, Zahra Chavoshzadeh, Seyed Alireza Mahdaviani, Taher Cheraghi, Nasrin Behniafard, Reza Amin, Soheila Aleyasin, Reza Faridhosseini, Farahzad Jabbari-Azad, Mohammamd Nabavi, Mohammad Hassan Bemanian, Saba Arshi, Rasol Molatefi, Roya Sherkat, Mahboubeh Mansouri, Mehrnaz Mesdaghi, Delara Babaie, Iraj Mohammadzadeh, Javad Ghaffari, Alireza Shafiei, Najmeddin Kalantari, Hamid Ahanchian, Maryam Khoshkhui, Habib Soheili, Abbas Dabbaghzadeh, Afshin Shirkani, Rasoul Nasiri Kalmarzi, Seyed Hamidreza Mortazavi, Javad Tafaroji, Abbas Khalili, Javad Mohammadi, Babak Negahdari, Mohammad-Taghi Joghataei, Basel K Al-Ramadi, Capucine Picard, Nima Parvaneh, Nima Rezaei, Talal A Chatila, Michel J Massaad, Sevgi Keles, Lennart Hammarström, Raif S Geha, Asghar Aghamohammadi
BACKGROUND: Combined immunodeficiencies (CIDs) are diseases of defective adaptive immunity with diverse clinical phenotypes. Although CIDs are more prevalent in the Middle East than Western countries, the resources for genetic diagnosis are limited. OBJECTIVES: This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically. METHODS: Clinical and laboratory data were obtained from 696 patients with CIDs...
September 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28861136/a-hands-on-activity-to-demonstrate-the-central-dogma-of-molecular-biology-via-a-simulated-vdj-recombination-activity
#8
Pamela A Marshall
No abstract text is available yet for this article.
2017: Journal of Microbiology & Biology Education: JMBE
https://www.readbyqxmd.com/read/28348365/e%C3%AE-and-3-rr-igh-enhancers-show-hierarchic-unilateral-dependence-in-mature-b-cells
#9
A Saintamand, C Vincent-Fabert, M Marquet, N Ghazzaui, V Magnone, E Pinaud, M Cogné, Y Denizot
Enhancer and super-enhancers are master regulators of cell fate. While they act at long-distances on adjacent genes, it is unclear whether they also act on one another. The immunoglobulin heavy chain (IgH) locus is unique in carrying two super-enhancers at both ends of the constant gene cluster: the 5'Eμ super-enhancer promotes VDJ recombination during the earliest steps of B-cell ontogeny while the 3' regulatory region (3'RR) is essential for late differentiation. Since they carry functional synergies in mature B-cells and physically interact during IgH locus DNA looping, we investigated if they were independent engines of locus remodelling or if their function was more intimately intermingled, their optimal activation then requiring physical contact with each other...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28294689/genomics-signaling-and-treatment-of-waldenstr%C3%A3-m-macroglobulinemia
#10
REVIEW
Zachary R Hunter, Guang Yang, Lian Xu, Xia Liu, Jorge J Castillo, Steven P Treon
Next-generation sequencing has revealed recurring somatic mutations in Waldenström macroglobulinemia (WM). Commonly recurring mutations include MYD88 (95% to 97%), CXCR4 (30% to 40%), ARID1A (17%), and CD79B (8% to 15%). Diagnostic discrimination of WM from overlapping B-cell malignancies is aided by MYD88 mutation status. Transcription is affected by MYD88 and CXCR4 mutations and includes overexpression of genes involved in VDJ recombination, CXCR4 pathway signaling, and BCL2 family members. Among patients with MYD88 mutations, those with CXCR4 mutations show transcriptional silencing of tumor suppressors associated with acquisition of mutated MYD88...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28256716/assessing-microenvironment-immunogenicity-using-tumor-specimen-exomes-co-detection-of-tcr-%C3%AE-%C3%AE-v-d-j-recombinations-correlates-with-pd-1-expression
#11
Yaping N Tu, Wei Lue Tong, Mohammad D Samy, John M Yavorski, Minjung Kim, George Blanck
T-cell receptor (TcR) recombinations can be recovered from tumor specimen, whole exome sequences (WXS) files. However, it is not yet clear how these recombinations represent lymphocytes or an anti-tumor immune response. Here we report the identification of productive TcR-β recombinations in WXS files representing primary and metastatic melanoma. The recombinations are identifiable in about 20% of the cancer genome atlas melanoma samples. This frequency of detection is lower than the frequency of TcR-α VJ recombinations, consistent with the occurrence of biallelic TcR-α recombinations and possibly consistent with the fact that only one junctional recombination is required for TcR-α whereas two recombinations are required to form a TcR-β gene...
June 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28196891/insights-into-immune-system-development-and-function-from-mouse-t-cell-repertoires
#12
Zachary Sethna, Yuval Elhanati, Chrissy S Dudgeon, Curtis G Callan, Arnold J Levine, Thierry Mora, Aleksandra M Walczak
The ability of the adaptive immune system to respond to arbitrary pathogens stems from the broad diversity of immune cell surface receptors. This diversity originates in a stochastic DNA editing process (VDJ recombination) that acts on the surface receptor gene each time a new immune cell is created from a stem cell. By analyzing T-cell receptor (TCR) sequence repertoires taken from the blood and thymus of mice of different ages, we quantify the changes in the VDJ recombination process that occur from embryo to young adult...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28169523/the-suv39h1-protein-lysine-methyltransferase-methylates-chromatin-proteins-involved-in-heterochromatin-formation-and-vdj-recombination
#13
Srikanth Kudithipudi, Maren Kirstin Schuhmacher, Adam Fiseha Kebede, Albert Jeltsch
SUV39H1 is an H3K9 methyltransferase involved in the formation of heterochromatin. We investigated its substrate specificity profile and show recognition of H3 residues between K4 and G12 with highly specific readout of R8. The specificity profile of SUV39H1 is distinct from its paralog SUV39H2, indicating that they can have different additional substrates. Using the specificity profile, several novel SUV39H1 candidate substrates were identified. We observed methylation of 19 novel substrates at the peptide level and for six of them at the protein level...
April 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28137913/chromatin-domain-organization-of-the-tcrb-locus-and-its-perturbation-by-ectopic-ctcf-binding
#14
Pratishtha Rawat, Manisha Jalan, Ananya Sadhu, Abhilasha Kanaujia, Madhulika Srivastava
CTCF-mediated chromatin interactions influence organization and function of mammalian genome in diverse ways. We analyzed the interactions among CTCF binding sites (CBS) at the murine TCRb locus to discern the role of CTCF-mediated interactions in the regulation of transcription and VDJ recombination. Chromosome conformation capture analysis revealed thymocyte-specific long-range intrachromosomal interactions among various CBS across the locus that were relevant for defining the limit of the enhancer Eb-regulated recombination center (RC) and for facilitating the spatial proximity of TCRb variable (V) gene segments to the RC...
May 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27995306/t-cell-receptor-gene-recombinations-in-human-tumor-specimen-exome-files-detection-of-t-cell-receptor-%C3%AE-vdj-recombinations-associates-with-a-favorable-oncologic-outcome-for-bladder-cancer
#15
Mohammad D Samy, Wei Lue Tong, John M Yavorski, Wade J Sexton, George Blanck
Understanding tumor-resident T cells is important for cancer prognosis and treatment options. Conventional, solid tumor specimen exome files can be searched directly for recombined T cell receptor (TcR)-α segments; RNASeq files can include TcR-β VDJ recombinations. To learn whether there are medically relevant uses of exome-based detection of TcR V(D)J recombinations in the tumor microenvironment, we searched cancer genome atlas and Moffitt Cancer Center, tumor specimen exome files for TcR-β, TcR-γ, and TcR-δ recombinations, for bladder and stomach cancer...
March 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27871274/chemotherapy-curable-malignancies-and-cancer-stem-cells-a-biological-review-and-hypothesis
#16
REVIEW
Philip Savage
BACKGROUND: Cytotoxic chemotherapy brings routine cures to only a small select group of metastatic malignancies comprising gestational trophoblast tumours, germ cell tumours, acute leukemia, Hodgkin's disease, high grade lymphomas and some of the rare childhood malignancies. We have previously postulated that the extreme sensitivity to chemotherapy for these malignancies is linked to the on-going high levels of apoptotic sensitivity that is naturally linked with the unique genetic events of nuclear fusion, meiosis, VDJ recombination, somatic hypermutation, and gastrulation that have occurred within the cells of origin of these malignancies...
November 21, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27686811/proteogenomics-for-the-comprehensive-analysis-of-human-cellular-and-serum-antibody-repertoires
#17
REVIEW
Paula Díez, Manuel Fuentes
The vast repertoire of immunoglobulins produced by the immune system is a consequence of the huge amount of antigens to which we are exposed every day. The diversity of these immunoglobulins is due to different mechanisms (including VDJ recombination, somatic hypermutation, and antigen selection). Understanding how the immune system is capable of generating this diversity and which are the molecular bases of the composition of immunoglobulins are key challenges in the immunological field. During the last decades, several techniques have emerged as promising strategies to achieve these goals, but it is their combination which appears to be the fruitful solution for increasing the knowledge about human cellular and serum antibody repertoires...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27472868/high-resolution-analysis-of-the-b-cell-repertoire-before-and-after-polyethylene-glycol-fusion-reveals-preferential-fusion-of-rare-antigen-specific-b-cells
#18
Axel R S X Dubois, Jean-Philippe Buerckert, Regina Sinner, William J Faison, Anne M Molitor, Claude P Muller
OBJECTIVE: The hybridoma technology is one of the most important advances in clinical immunology. Little is known about the differences between the antibodies produced during the in vivo immune response and those recovered in hybridoma libraries. Here, we investigate a potential fusion bias inherent to the hybridoma production process. METHODS: Transgenic rats carrying human Ig heavy and light chain loci were immunized with measles virus (MV) to generate human mAbs...
June 8, 2016: Human Antibodies
https://www.readbyqxmd.com/read/27301862/transcriptome-sequencing-reveals-a-profile-that-corresponds-to-genomic-variants-in-waldenstr%C3%A3-m-macroglobulinemia
#19
Zachary R Hunter, Lian Xu, Guang Yang, Nicholas Tsakmaklis, Josephine M Vos, Xia Liu, Jie Chen, Robert J Manning, Jiaji G Chen, Philip Brodsky, Christopher J Patterson, Joshua Gustine, Toni Dubeau, Jorge J Castillo, Kenneth C Anderson, Nikhil M Munshi, Steven P Treon
Whole-genome sequencing has identified highly prevalent somatic mutations including MYD88, CXCR4, and ARID1A in Waldenström macroglobulinemia (WM). The impact of these and other somatic mutations on transcriptional regulation in WM remains to be clarified. We performed next-generation transcriptional profiling in 57 WM patients and compared findings to healthy donor B cells. Compared with healthy donors, WM patient samples showed greatly enhanced expression of the VDJ recombination genes DNTT, RAG1, and RAG2, but not AICDA Genes related to CXCR4 signaling were also upregulated and included CXCR4, CXCL12, and VCAM1 regardless of CXCR4 mutation status, indicating a potential role for CXCR4 signaling in all WM patients...
August 11, 2016: Blood
https://www.readbyqxmd.com/read/27264181/two-mutually-exclusive-local-chromatin-states-drive-efficient-v-d-j-recombination
#20
Daniel J Bolland, Hashem Koohy, Andrew L Wood, Louise S Matheson, Felix Krueger, Michael J T Stubbington, Amanda Baizan-Edge, Peter Chovanec, Bryony A Stubbs, Kristina Tabbada, Simon R Andrews, Mikhail Spivakov, Anne E Corcoran
Variable (V), diversity (D), and joining (J) (V(D)J) recombination is the first determinant of antigen receptor diversity. Understanding how recombination is regulated requires a comprehensive, unbiased readout of V gene usage. We have developed VDJ sequencing (VDJ-seq), a DNA-based next-generation-sequencing technique that quantitatively profiles recombination products. We reveal a 200-fold range of recombination efficiency among recombining V genes in the primary mouse Igh repertoire. We used machine learning to integrate these data with local chromatin profiles to identify combinatorial patterns of epigenetic features that associate with active VH gene recombination...
June 14, 2016: Cell Reports
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