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V(d)J recombination

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https://www.readbyqxmd.com/read/28630107/pillars-article-a-role-for-histone-acetylation-in-the-developmental-regulation-of-v-d-j-recombination-science-2000-287-495-498
#1
Michelle Taylor McMurry, Michael S Krangel
No abstract text is available yet for this article.
July 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28612717/-paralogy-and-redundancy-maintaining-genome-integrity-during-v-d-j-recombination
#2
Chloé Lescale, Hélène Lenden Hasse, Ludovic Deriano
No abstract text is available yet for this article.
May 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28610800/human-igg-repertoire-of-malaria-antigen-immunized-human-immune-system-his-mice
#3
Raquel Tayar Nogueira, Vincent Sahi, Jing Huang, Moriya Tsuji
Humanized mouse models present an important tool for preclinical evaluation of new vaccines and therapeutics. Here we show the human variable repertoire of antibody sequences cloned from a previously described human immune system (HIS) mouse model that possesses functional human CD4+ T cells and B cells, namely HIS-CD4/B mice. We sequenced variable IgG genes from single memory B-cell and plasma-cell sorted from splenocytes or whole blood lymphocytes of HIS-CD4/B mice that were vaccinated with a human plasmodial antigen, a recombinant Plasmodium falciparum circumsporozoite protein (rPfCSP)...
June 10, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28606698/comparative-analyses-of-whole-genome-sequences-of-leishmania-infantum-isolates-from-humans-and-dogs-in-northeastern-brazil
#4
D G Teixeira, G R G Monteiro, D R A Martins, M Z Fernandes, V Macedo-Silva, M Ansaldi, P R P Nascimento, M A Kurtz, J A Streit, M F F M Ximenes, R D Pearson, A Miles, J M Blackwell, M E Wilson, A Kitchen, J E Donelson, J P M S Lima, S M B Jeronimo
The genomic sequences of 20 Leishmania infantum isolates collected in northeastern Brazil were compared with each other and with the available genomic sequences of 29 L. infantum/donovani isolates from Nepal and Turkey. The Brazilian isolates were obtained in the early 1990s or since 2009 from patients with visceral or non-ulcerating cutaneous leishmaniasis, asymptomatic humans, or dogs with visceral leishmaniasis. Two isolates were from the blood and bone marrow of the same visceral leishmaniasis patient. All 20 genomic sequences display 99...
June 10, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28591585/tcrd-rearrangement-redirects-a-processive-tcra-recombination-program-to-expand-the-tcra-repertoire
#5
Zachary M Carico, Kingshuk Roy Choudhury, Baojun Zhang, Yuan Zhuang, Michael S Krangel
Adaptive immunity depends on diverse T cell receptor repertoires generated by variable, diversity, and joining (V[D]J) recombination. Here, we define the principles by which combinatorial diversity is generated in the murine Tcra repertoire. Tcra and Tcrd gene segments share the Tcra-Tcrd locus, with interspersed Vα and Vδ segments undergoing Vδ-Dδ-Jδ rearrangement in CD4(-)CD8(-) thymocytes and then multiple rounds of Vα-Jα rearrangement in CD4(+)CD8(+) thymocytes. We document stepwise, highly coordinated proximal-to-distal progressions of Vα and Jα use on individual Tcra alleles, limiting combinatorial diversity...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28588062/secondary-somatic-mutations-restoring-rad51c-and-rad51d-associated-with-acquired-resistance-to-the-parp-inhibitor-rucaparib-in-high-grade-ovarian-carcinoma
#6
Olga Kondrashova, Minh Nguyen, Kristy Shield-Artin, Anna V Tinker, Nelson N H Teng, Maria I Harrell, Michael J Kuiper, Gwo-Yaw Ho, Holly Barker, Maria Jasin, Rohit Prakash, Elizabeth M Kass, Meghan R Sullivan, Gregory J Brunette, Kara A Bernstein, Robert L Coleman, Anne Floquet, Michael Friedlander, Ganessan Kichenadasse, David M O'Malley, Amit M Oza, James X Sun, Liliane Robillard, Lara Maloney, David D L Bowtell, Heidi Giordano, Matthew J Wakefield, Scott H Kaufmann, Andrew D Simmons, Thomas C Harding, Mitch Raponi, Iain A McNeish, Elizabeth M Swisher, Kevin Lin, Clare L Scott
High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC...
June 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28571041/cbf1-is-clinically-prognostic-and-serves-as-a-target-to-block-cellular-invasion-and-chemoresistance-of-emt-like-glioblastoma-cells
#7
D Maciaczyk, D Picard, L Zhao, K Koch, D Herrera-Rios, G Li, V Marquardt, D Pauck, T Hoerbelt, W Zhang, D M Ouwens, M Remke, T Jiang, H J Steiger, J Maciaczyk, U D Kahlert
BACKGROUND: Glioblastoma is the most common and most lethal primary brain cancer. CBF1 (also known as Recombination signal Binding Protein for immunoglobulin kappa J, RBPJ) is the cardinal transcriptional regulator of the Notch signalling network and has been shown to promote cancer stem-like cells (CSCs) in glioblastoma. Recent studies suggest that some of the malignant properties of CSCs are mediated through the activation of pro-invasive programme of epithelial-to-mesenchymal transition (EMT)...
June 1, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28569776/hiv-integrase-inhibitor-elvitegravir-impairs-rag-functions-and-inhibits-v-d-j-recombination
#8
Mayilaadumveettil Nishana, Namrata M Nilavar, Rupa Kumari, Monica Pandey, Sathees C Raghavan
Integrase inhibitors are a class of antiretroviral drugs used for the treatment of AIDS that target HIV integrase, an enzyme responsible for integration of viral cDNA into host genome. RAG1, a critical enzyme involved in V(D)J recombination exhibits structural similarity to HIV integrase. We find that two integrase inhibitors, Raltegravir and Elvitegravir, interfered with the physiological functions of RAGs such as binding, cleavage and hairpin formation at the recombination signal sequence (RSS), though the effect of Raltegravir was limited...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28550350/recent-advances-in-the-study-of-immunodeficiency-and-dna-damage-response
#9
REVIEW
Tomohiro Morio
DNA breaks can be induced by exogenous stimuli or by endogenous stress, but are also generated during recombination of V, D, and J genes (V(D)J recombination), immunoglobulin class switch recombination (CSR). Among various DNA breaks generated, DNA double strand break (DSB) is the most deleterious one. DNA damage response (DDR) is initiated when DSBs are detected, leading to DNA break repair by non-homologous end joining (NHEJ). The process is critically important for the generation of diversity for foreign antigens; and failure to exert DNA repair leads to immunodeficiency such as severe combined immunodeficiency and hyper-IgM syndrome...
May 26, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28539926/gene-specific-substitution-profiles-describe-the-types-and-frequencies-of-amino-acid-changes-during-antibody-somatic-hypermutation
#10
Zizhang Sheng, Chaim A Schramm, Rui Kong, James C Mullikin, John R Mascola, Peter D Kwong, Lawrence Shapiro
Somatic hypermutation (SHM) plays a critical role in the maturation of antibodies, optimizing recognition initiated by recombination of V(D)J genes. Previous studies have shown that the propensity to mutate is modulated by the context of surrounding nucleotides and that SHM machinery generates biased substitutions. To investigate the intrinsic mutation frequency and substitution bias of SHMs at the amino acid level, we analyzed functional human antibody repertoires and developed mGSSP (method for gene-specific substitution profile), a method to construct amino acid substitution profiles from next-generation sequencing-determined B cell transcripts...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28532656/the-il-33-st2-axis-is-crucial-in-type-2-airway-responses-induced-by-the-staphylococcus-aureus-protease-spld
#11
Andrea R Teufelberger, Maria Nordengrün, Harald Braun, Tania Maes, Katrien De Grove, Gabriele Holtappels, Clara O'Brien, Sharen Provoost, Hamida Hammad, Amanda Gonçalves, Rudi Beyaert, Wim Declercq, Peter Vandenabeele, Dmitri V Krysko, Barbara M Bröker, Claus Bachert, Olga Krysko
BACKGROUND: Chronic airway inflammatory diseases such as chronic rhinosinusitis with nasal polyps and asthma showed increased nasal Staphylococcus aureus (S. aureus) colonization. Serine protease like protein D (SplD) and other closely related proteases secreted by S. aureus have recently been identified as inducers of allergic asthma in humans and mice but their mechanism of action is largely unknown. OBJECTIVE: We investigated the role of recombinant SplD in driving Th2-biased responses and IgE formation in a murine model of allergic asthma...
May 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28532625/v-d-j-recombination-exploits-dna-damage-responses-to-promote-immunity
#12
REVIEW
Rahul Arya, Craig H Bassing
It has been recognized for 40 years that the variable (diversity) joining [V(D)J] recombination-mediated assembly of diverse B and T lymphocyte antigen receptor (AgR) genes is not only essential for adaptive immunity, but also a risk for autoimmunity and lymphoid malignancies. Over the past few years, several studies have revealed that recombination-activating gene (RAG) endonuclease-induced DNA double-strand breaks (DSBs) transcend hazardous intermediates during antigen receptor gene assembly. RAG cleavage within the genomes of lymphocyte progenitors and immature lymphocytes regulates the expression of ubiquitous and lymphocyte-specific gene transcripts to control the differentiation and function of both adaptive and innate immune cell lineages...
May 19, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28515723/different-somatic-hypermutation-levels-among-antibody-subclasses-disclosed-by-a-new-next-generation-sequencing-based-antibody-repertoire-analysis
#13
Kazutaka Kitaura, Hiroshi Yamashita, Hitomi Ayabe, Tadasu Shini, Takaji Matsutani, Ryuji Suzuki
A diverse antibody repertoire is primarily generated by the rearrangement of V, D, and J genes and subsequent somatic hypermutation (SHM). Class-switch recombination (CSR) produces various isotypes and subclasses with different functional properties. Although antibody isotypes and subclasses are considered to be produced by both direct and sequential CSR, it is still not fully understood how SHMs accumulate during the process in which antibody subclasses are generated. Here, we developed a new next-generation sequencing (NGS)-based antibody repertoire analysis capable of identifying all antibody isotype and subclass genes and used it to examine the peripheral blood mononuclear cells of 12 healthy individuals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28515153/differential-regulation-of-renal-klotho-and-fgfr1-in-normal-and-uremic-rats
#14
Juan R Muñoz-Castañeda, Carmen Herencia, Maria Victoria Pendón-Ruiz de Mier, Maria Encarnación Rodriguez-Ortiz, Juan M Diaz-Tocados, Noemi Vergara, Julio M Martínez-Moreno, Maria Dolores Salmerón, William G Richards, Arnold Felsenfeld, Makoto Kuro-O, Yolanda Almadén, Mariano Rodríguez
In renal failure, hyperphosphatemia occurs despite a marked elevation in serum fibroblast growth factor (FGF)-23. Abnormal regulation of the FGFR1-Klotho receptor complex may cause a resistance to the phosphaturic action of FGF23. The purpose of the present study was to investigate the regulation of renal Klotho and FGF receptor (FEFR)-1 in healthy and uremic rats induced by 5/6 nephrectomy. In normal rats, the infusion of rat recombinant FGF23 enhanced phosphaturia and increased renal FGFR1 expression; however, Klotho expression was reduced...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28482040/transposition-of-mutator-like-transposable-elements-mules-resembles-hat-and-transib-elements-and-v-d-j-recombination
#15
Kun Liu, Susan R Wessler
Mutator-like transposable elements (MULEs) are widespread across fungal, plant and animal species. Despite their abundance and importance as genetic tools in plants, the transposition mechanism of the MULE superfamily was previously unknown. Discovery of the Muta1 element from Aedes aegypti and its successful transposition in yeast facilitated the characterization of key steps in Muta1 transposition. Here we show that purified transposase binds specifically to the Muta1 ends and catalyzes excision through double strand breaks (DSB) and the joining of newly excised transposon ends with target DNA...
May 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28467808/a-systematic-approach-for-peptide-characterization-of-b-cell-receptor-in-chronic-lymphocytic-leukemia-cells
#16
Paula Díez, Nieves Ibarrola, Rosa M Dégano, Quentin Lécrevisse, Arancha Rodriguez-Caballero, Ignacio Criado, Wendy G Nieto, Rafael Góngora, Marcos González, Julia Almeida, Alberto Orfao, Manuel Fuentes
A wide variety of immunoglobulins (Ig) is produced by the immune system thanks to different mechanisms (V(D)J recombination, somatic hypermutation, and antigen selection). The profiling of Ig sequences (at both DNA and peptide levels) are of great relevance to developing targeted vaccines or treatments for specific diseases or infections. Thus, genomics and proteomics techniques (such as Next-Generation Sequencing (NGS) and mass spectrometry (MS)) have notably increased the knowledge in Ig sequencing and serum Ig peptide profiling in a high-throughput manner...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28466095/survival-of-the-fetus-fetal-b-and-t-cell-receptor-repertoire-development
#17
REVIEW
Erez Rechavi, Raz Somech
A mature and diverse T and B cell receptor repertoire is a prerequisite for immunocompetence. In light of its increased susceptibility to infection, the human fetus has long been considered deficient in this regard. However, data accumulated since the 1990s and in earnest in the past couple of years paints a more complicated picture. As we describe in this review, mechanisms responsible for generating a diverse receptor repertoire, such as somatic recombination, class switch recombination, and somatic hypermutation, are all operational to surprising extents in the growing fetus...
May 2, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28461573/genetic-and-small-molecule-disruption-of-the-aid-rad51-axis-similarly-protects-nonobese-diabetic-mice-from-type-1-diabetes-through-expansion-of-regulatory-b-lymphocytes
#18
Jeremy J Ratiu, Jeremy J Racine, Muneer G Hasham, Qiming Wang, Jane A Branca, Harold D Chapman, Jing Zhu, Nina Donghia, Vivek Philip, William H Schott, Clive Wasserfall, Mark A Atkinson, Kevin D Mills, Caroline M Leeth, David V Serreze
B lymphocytes play a key role in type 1 diabetes (T1D) development by serving as a subset of APCs preferentially supporting the expansion of autoreactive pathogenic T cells. As a result of their pathogenic importance, B lymphocyte-targeted therapies have received considerable interest as potential T1D interventions. Unfortunately, the B lymphocyte-directed T1D interventions tested to date failed to halt β cell demise. IgG autoantibodies marking humans at future risk for T1D indicate that B lymphocytes producing them have undergone the affinity-maturation processes of class switch recombination and, possibly, somatic hypermutation...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28458212/accumulation-elimination-sequestration-and-genetic-variation-of-lead-pb-2-loads-within-and-between-generations-of-drosophila-melanogaster
#19
Elizabeth K Peterson, Diane T Wilson, Bernard Possidente, Phillip McDaniel, Eric J Morley, Debra Possidente, Kurt T Hollocher, Douglas M Ruden, Helmut V B Hirsch
We examined accumulation, sequestration, elimination, and genetic variation for lead (Pb) loads within and between generations of Drosophila melanogaster. Flies were reared in control or leaded medium at various doses and tested for their Pb loads at different stages of development (larvae, eclosion, newly-eclosed adults, and mature adults). Pb loads were tested using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). We found that D. melanogaster readily accumulated Pb throughout their lifespan and the levels of accumulation increased with Pb exposure in the medium...
April 21, 2017: Chemosphere
https://www.readbyqxmd.com/read/28454980/are-the-results-of-intravenous-thrombolysis-trials-reproduced-in-clinical-practice-comparison-of-observed-and-expected-outcomes-with-the-stroke-thrombolytic-predictive-instrument-stpi
#20
A Decourcelle, S Moulin, N Dequatre-Ponchelle, M Bodenant, C Rossi, M Girot, H Hénon, E Wiel, R Bordet, P Goldstein, J P Pruvo, C Cordonnier, D Leys
AIM: In patients with cerebral ischemia, intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) increases survival without handicap or dependency despite an increased risk of bleeding. This study evaluated whether the results of randomized controlled trials are reproduced in clinical practice. METHOD: Data from a registry of consecutive patients treated by rt-PA at Lille University Hospital were retrospectively analyzed for outcomes, using modified Rankin Scale (mRS) scores, at 3 months...
April 25, 2017: Revue Neurologique
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