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V(d)J recombination

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https://www.readbyqxmd.com/read/29457375/evidence-for-alternate-modes-of-b-cell-activation-involving-fab-acquired-n-glycosylations-in-antibody-secreting-cells-infiltrating-the-labial-salivary-glands-of-sj%C3%A3-gren-s-syndrome-patients
#1
Kristi A Koelsch, Joshua Cavett, Kenneth Smith, Jacen S Moore, Sylvain D Lehoux, Nan Jia, Tim Mather, Syed M S Quadri, Astrid Rasmussen, C Erick Kaufman, David M Lewis, Lida Radfar, Teresa A Scordino, Christopher J Lessard, Biji T Kurien, Richard D Cummings, Judith A James, Kathy L Sivils, A Darise Farris, R Hal Scofield
OBJECTIVE: To better understand the role of B cells, potential mechanisms for their aberrant activation, and the production of autoantibodies in the pathogenesis of Sjögren's Syndrome (SS), we explored selection pressures and N-glycosylation acquired by somatic mutation (acN-glyc) in the immunoglobulin (Ig) variable regions (V-regions) of antibody secreting cells (ASCs) isolated from the minor salivary glands of SS patients and non-SS controls with sicca symptoms. METHODS: We report a novel method to produce and characterize recombinant monoclonal antibodies (mAbs) from SS patient and control labial salivary gland single-cell sorted ASC infiltrates that can be utilized to concurrently probe any other expressed genes...
February 18, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29455846/the-unusual-genetics-and-biochemistry-of-bovine-immunoglobulins
#2
Robyn L Stanfield, Jeremy Haakenson, Thaddeus C Deiss, Michael F Criscitiello, Ian A Wilson, Vaughn V Smider
Antibodies are the key circulating molecules that have evolved to fight infection by the adaptive immune system of vertebrates. Typical antibodies of most species contain six complementarity-determining regions (CDRs), where the third CDR of the heavy chain (CDR H3) has the greatest diversity and often makes the most significant contact with antigen. Generally, the process of V(D)J recombination produces a vast repertoire of antibodies; multiple V, D, and J gene segments recombine with additional junctional diversity at the V-D and D-J joints, and additional combinatorial possibilities occur through heavy- and light-chain pairing...
2018: Advances in Immunology
https://www.readbyqxmd.com/read/29446083/development-and-clinical-characterization-of-a-novel-2041-liquid-filled-ionization-chambers-array-for-high-resolution-verification-of-radiotherapy-treatments
#3
L Brualla-González, A Vázquez-Luque, M Zapata, D M González-Castaño, V Luna-Vega, J Guiu-Souto, J Prieto-Pena, T García, D Granero, A Vicedo, J Rosellò, M Pombar, F Gómez, J Pardo-Montero
PURPOSE: To present a novel 2041 liquid-filled ionization chamber array for high-resolution verification of radiotherapy treatments. MATERIALS AND METHODS: The prototype has 2041 ionization chambers of 2.5×2.5 mm 2 area filled with isooctane. The detection elements are arranged in a central square grid of 43×43, totally covering an area of 107.5×107.5 mm 2 . The central inline and crossline are extended to 227 mm and the diagonals to 321 mm in order to be able to perform profile measurements of large fields...
February 15, 2018: Medical Physics
https://www.readbyqxmd.com/read/29431562/ionizing-radiation-does-not-impair-the-mechanisms-controlling-genetic-stability-during-t-cell-receptor-gene-rearrangement-in-mice
#4
Serge M Candéias, Sylwia Kabacik, Ann-Karin Olsen, Dag M Eide, Dag A Brede, Simon Bouffler, Christophe Badie
PURPOSE: To determine whether low dose/low dose rate radiation-induced genetic instability may result from radiation-induced inactivation of mechanisms induced by the ATM-dependent DNA damage response checkpoint. To this end, we analysed the faithfulness of T cell receptor (TR) gene rearrangement by V(D)J recombination in DNA from mice exposed to a single dose of X-ray or chronically exposed to low dose rate γ radiation. MATERIALS AND METHODS: Genomic DNA obtained from the blood or the thymus of wild type or Ogg1-deficient mice exposed to low (0...
February 12, 2018: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29410330/plasmablast-antibody-repertoires-in-elderly-influenza-vaccine-responders-exhibit-restricted-diversity-but-increased-breadth-of-binding-across-influenza-strains
#5
Chia-Hsin Ju, Lisa K Blum, Sarah Kongpachith, Nithya Lingampalli, Rong Mao, Petter Brodin, Cornelia L Dekker, Mark M Davis, William H Robinson
Seasonal influenza vaccines elicit antibody responses that can prevent infection, but their efficacy is reduced in the elderly. While a subset of elderly individuals can still mount sufficient vaccine-induced antibody responses, little is known about the properties of the vaccine-induced antibody repertoires in elderly as compared to young responders. To gain insights into the effects of aging on influenza vaccine-induced antibody responses, we used flow cytometry and a cell-barcoding method to sequence antibody heavy and light chain gene pairs expressed by individual blood plasmablasts generated in response to influenza vaccination in elderly (aged 70-89) and young (aged 20-29) responders...
February 1, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29361128/variable-rates-of-simple-satellite-gains-across-the-drosophila-phylogeny
#6
Kevin H-C Wei, Sarah E Lower, Ian V Caldas, Trevor J Sless, Daniel A Barbash, Andrew G Clark
Simple satellites are tandemly repeating short DNA motifs that can span megabases in eukaryotic genomes. Because they can cause genomic instability through non-allelic homologous exchange, they are primarily found in the repressive heterochromatin near centromeres and telomeres where recombination is minimal, and on the Y chromosome, where they accumulate as the chromosome degenerates. Interestingly, the types and abundances of simple satellites often vary dramatically between closely related species, suggesting that they turn over rapidly...
January 19, 2018: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29361059/t-cell-receptor-%C3%AE-recombinations-in-renal-cell-carcinoma-exome-files-correlate-with-an-intermediate-level-of-t-cell-exhaustion-biomarkers
#7
Anne T Mai, Wei Lue Tong, Yaping N Tu, George Blanck
Renal cell carcinoma exome-derived, V(D)J recombination reads had an elevated presence and variability, for both TcR-α and β, when compared to marginal tissue, reflecting an opportunity to assess tumor immunogenicity by comparison with marginal tissue T-cells. PD-1, PD-L2, CTLA4, and FOXP3, all of which are implicated in the evasion of an anti-tumor immune response, had a significantly higher expression for samples representing co-detection of productive TcR-⍺ and -β recombination reads. Samples representing tumors with productive TcR-α recombination reads but no detectable, productive TcR-β recombination reads, reflected a 20% survival advantage, and RNASeq data indicated an intermediate level of immune checkpoint gene expression for those samples...
January 18, 2018: International Immunology
https://www.readbyqxmd.com/read/29357100/autodisplay-of-an-avidin-with-biotin-binding-activity-on-the-surface-of-escherichia-coli
#8
H D Pardavé-Alejandre, J E Alvarado-Yaah, E N Pompa-Mera, J E Muñoz-Medina, B Sárquiz-Martínez, C E Santacruz-Tinoco, R G Manning-Cela, V Ortíz-Navarrete, C López-Macías, C R González-Bonilla
OBJECTIVES: To display a recombinant avidin fused to the autotransporter ShdA to bind biotinylated molecules on the surface of Escherichia coli. RESULTS: Two chimeric protein constructs containing avidin fused to the autotransporter ShdA were expressed on the surface of Escherichia coli DH5α. One fusion protein contained 476 amino acids of the ShdA α and β domains, whereas the second consisted of a 314 amino acid from α and truncated β domains. Protein production was verified by SDS-PAGE using an antibody to the molecular FLAG-tag...
January 22, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29345601/vaccine-effectiveness-and-use-of-collar-impregnated-with-insecticide-for-reducing-incidence-of-leishmania-infection-in-dogs-in-an-endemic-region-for-visceral-leishmaniasis-in-brazil
#9
E G Lopes, A P Sevá, F Ferreira, C M Nunes, L B Keid, R M Hiramoto, H L Ferreira, T M F S Oliveira, F G Ovallos, E A B Galati, T J Villegas, D V Bortoletto, S Y O B Valadas, R M Soares
Although a national programme for control of visceral leishmaniosis (VL) is being run in Brazil, the disease continues to spread. This programme is essentially based on culling infected dogs from endemic regions. Thus, there is an urgent need to develop other control measures against VL to deter its advance. Here, a subunit vaccine, a recombinant vaccine, an insecticide-impregnated collar and the associations between these measures were evaluated for reducing the incidence of Leishmania infection in dogs. This was through a cohort study conducted in an endemic region of Brazil, considering the incidence and time of total exposure over a period of 1 year...
January 18, 2018: Epidemiology and Infection
https://www.readbyqxmd.com/read/29344353/effects-of-tnf-receptor-blockade-on-in-vitro-cell-survival-and-response-to-negative-energy-balance-in-dairy-cattle
#10
C A Martel, L K Mamedova, J E Minton, M Garcia, C Legallet, B J Bradford
Background: Associative data and some controlled studies suggest that the inflammatory cytokine tumor necrosis factor (TNF) α can induce fatty liver in dairy cattle. However, research demonstrating that TNFα is a necessary component in the etiology of bovine fatty liver is lacking. The aim of this work was to evaluate whether blocking TNFα signaling with a synthetic cyclic peptide (TNF receptor loop peptide; TRLP) would improve liver metabolic function and reduce triglyceride accumulation during feed restriction...
2018: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29336845/defining-b-cell-chromatin-lessons-from-ebf1
#11
REVIEW
Sören Boller, Rui Li, Rudolf Grosschedl
Hematopoiesis is regulated by signals from the microenvironment, transcription factor networks, and changes of the epigenetic landscape. Transcription factors interact with and shape chromatin to allow for lineage- and cell type-specific changes in gene expression. During B lymphopoiesis, epigenetic regulation is observed in multilineage progenitors in which a specific chromatin context is established, at the onset of the B cell differentiation when early B cell factor 1 (EBF1) induces lineage-specific changes in chromatin, during V(D)J recombination and after antigen-driven activation of B cells and terminal differentiation...
January 11, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29295910/range-expansion-and-the-origin-of-usa300-north-american-epidemic-methicillin-resistant-staphylococcus-aureus
#12
Lavanya Challagundla, Xiao Luo, Isabella A Tickler, Xavier Didelot, David C Coleman, Anna C Shore, Geoffrey W Coombs, Daniel O Sordelli, Eric L Brown, Robert Skov, Anders Rhod Larsen, Jinnethe Reyes, Iraida E Robledo, Guillermo J Vazquez, Raul Rivera, Paul D Fey, Kurt Stevenson, Shu-Hua Wang, Barry N Kreiswirth, Jose R Mediavilla, Cesar A Arias, Paul J Planet, Rathel L Nolan, Fred C Tenover, Richard V Goering, D Ashley Robinson
The USA300 North American epidemic (USA300-NAE) clone of methicillin-resistant Staphylococcus aureus has caused a wave of severe skin and soft tissue infections in the United States since it emerged in the early 2000s, but its geographic origin is obscure. Here we use the population genomic signatures expected from the serial founder effects of a geographic range expansion to infer the origin of USA300-NAE and identify polymorphisms associated with its spread. Genome sequences from 357 isolates from 22 U.S...
January 2, 2018: MBio
https://www.readbyqxmd.com/read/29241731/efficacy-of-lentiviral-mediated-gene-therapy-in-an-omenn-syndrome-rag2-mouse-model-is-not-hindered-by-inflammation-and-immune-dysregulation
#13
Valentina Capo, Maria Carmina Castiello, Elena Fontana, Sara Penna, Marita Bosticardo, Elena Draghici, Luigi P Poliani, Lucia Sergi Sergi, Rosita Rigoni, Barbara Cassani, Monica Zanussi, Paola Carrera, Paolo Uva, Kerry Dobbs, Nicolò Sacchetti, Luigi D Notarangelo, Niek P van Til, Gerard Wagemaker, Anna Villa
BACKGROUND: Omenn syndrome (OS) is a rare severe combined immunodeficiency associated with autoimmunity, caused by defects of the lymphoid-specific V(D)J recombination. Most patients carry hypomorphic mutations in recombination activating genes (RAG) 1 or 2. Hematopoietic stem cell (HSC) transplantation is the standard treatment, however gene therapy (GT) may represent a valid alternative, especially for patients lacking a matched donor. OBJECTIVE: To determine the efficacy of lentiviral vector (LV) mediated GT in the murine model of OS (Rag2R229Q/R229Q) in correcting immunodeficiency and autoimmunity...
December 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29232168/high-throughput-screening-approach-for-identifying-compounds-that-inhibit-nonhomologous-end-joining
#14
Andrea L Bredemeyer, Bruce S Edwards, Mark K Haynes, Abigail J Morales, Yinan Wang, Oleg Ursu, Anna Waller, Larry A Sklar, Barry P Sleckman
DNA double-strand breaks (DSBs) are repaired primarily by homologous recombination (HR) or nonhomologous end joining (NHEJ). Compounds that modulate HR have shown promise as cancer therapeutics. The V(D)J recombination reaction, which assembles antigen receptor genes in lymphocytes, is initiated by the introduction of DNA DSBs at two recombining gene segments by the RAG endonuclease, followed by the NHEJ-mediated repair of these DSBs. Here, using HyperCyt automated flow cytometry, we develop a robust high-throughput screening (HTS) assay for NHEJ that utilizes engineered pre-B-cell lines where the V(D)J recombination reaction can be induced and monitored at a single-cell level...
December 1, 2017: SLAS Discovery
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
#15
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/29176980/iragu-a-novel-inducible-and-reversible-mouse-model-for-ubiquitous-recombinase-activity
#16
Marie Bonnet, Leonor Morais Sarmento, Ana C Martins, Daniel Sobral, Joana Silva, Jocelyne Demengeot
Developing lymphocytes express the recombination activating genes (RAGs) 1 and 2 products that form a site specific recombinase complex (RAG), introducing double strand DNA breaks (DSBs) at recombination signal sequences (RSSs) flanking the V, D, and J gene segments in the antigen receptor loci. The subsequent steps in the reaction consist in the ligation of DSBs by ubiquitous enzymes of the non-homologous end joining DNA repair pathway. This mutagenesis process is responsible for the generation of the very large clonal diversity of T and B lymphocytes, itself allowing the recognition of a virtually open-ended antigenic universe...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29175053/the-evolutionary-conservation-of-the-bidirectional-activity-of-the-nwc-gene-promoter-in-jawed-vertebrates-and-the-domestication-of-the-rag-transposon
#17
Lukasz Sniezewski, Sylwia Janik, Agnieszka Laszkiewicz, Michal Majkowski, Pawel Kisielow, Malgorzata Cebrat
The RAG-1 and RAG-2 genes form a recombinase complex that is indispensable for V(D)J recombination, which generates the diversity of immunoglobulins and T-cell receptors. It is widely accepted that the presence of RAGs in the genomes of jawed vertebrates and other lineages is a result of the horizontal transfer of a mobile genetic element. While a substantial amount of evidence has been gathered that clarifies the nature of the RAG transposon, far less attention has been paid to the genomic site of its integration in various host organisms...
November 22, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29143737/validation-of-elisa-methods-for%C3%A2-quantification-of-the-major-birch-allergen-bet-v-1-bsp090
#18
S Kaul, J Zimmer, O Dehus, A Constanzo, A DaasConstanzo, K-H Buchheit, J Asturias, M C Arilla, D Barber, A Bertocchi, B Brunetto, J A Carnes, M Chapman, G Chaudemanche, J Dayan-Kenigsberg, S Döring, F Führer, M T Gallego, P Iacovacci, K M Hanschmann, T Holzhauser, M Hrabina, A Ledesma, P Moingeon, E Nony, C Pini, G Plunkett, M Raulf, G Reese, E Sandberg, I Sander, B Smith, D Strecker, C Valerio, R van Ree, B Weber, S Vieths
To date, the potency of allergen products in Europe is expressed in manufacturer-specific units relative to a product-specific in-house reference. Consequently, cross-product comparability of allergen products from different manufacturers with respect to strength and efficacy is impossible. The Biological Standardisation Programme (BSP) project BSP090 addresses this issue via the establishment of reference standards in conjunction with ELISA methods for the quantification of major allergens in allergen products...
2017: Pharmeuropa Bio & Scientific Notes
https://www.readbyqxmd.com/read/29138356/the-soluble-pro-renin-receptor-does-not-influence-lithium-induced-diabetes-insipidus-but-does-provoke-beiging-of-white-adipose-tissue-in-mice
#19
Kevin T Yang, Fei Wang, Xiaohan Lu, Kexin Peng, Tianxin Yang, J David Symons
Earlier we reported that the recombinant soluble (pro) renin receptor sPRR-His upregulates renal aquoporin-2 (AQP2) expression, and attenuates polyuria associated with nephrogenic diabetes insipidus (NDI) induced by vasopressin type 2 receptor (V2R) antagonism. Patients that receive lithium therapy develop polyuria associated NDI that might be secondary to downregulation of renal AQP2. We hypothesized that sPRR-His attenuates indices of NDI associated with lithium treatment. Eight-week-old male C57/BL6 mice consumed chow supplemented with LiCl (40 mmol/kg diets) for 14 days...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29126456/virological-response-hiv-1-drug-resistance-mutations-and-genetic-diversity-among-patients-on-first-line-antiretroviral-therapy-in-n-djamena-chad-findings-from-a-cross-sectional-study
#20
Chatté Adawaye, Joseph Fokam, Erick Kamangu, Hamit Mahamat Alio, Aoudalkarim Moussa Chahad, Fabrice Susin, Ali Mahamat Moussa, Tchombou Hig-Zounet Bertin, Abdelsalam Tidjani, Dolores Vaira, Michel Moutschen
BACKGROUND: The national antiretroviral therapy in the Republic of Chad provides free of charge antiretroviral regimens and therapeutic monitoring for patients receiving antiretroviral therapy nationwide. For a successful programmatic uptake, these efforts merit to be supported by thorough assessments of antiretroviral therapy response and HIV-1 drug resistance surveillance, especially with risks of cross-resistance due to the gradual stavudine phasing out in such national settings. We therefore evaluated the virological response to antiretroviral therapy, HIV-1 drug resistance emergence and circulating HIV-1 clades in a Chad context...
November 10, 2017: BMC Research Notes
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