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https://www.readbyqxmd.com/read/28641141/rag2-involves-the-ig%C3%AE%C2%BA-locus-demethylation-during-b-cell-development
#1
Caijun Wu, Yanying Dong, Xiaohui Zhao, Ping Zhang, Mingzhe Zheng, Hua Zhang, Shichang Li, Yaofeng Jin, Yunfeng Ma, Huixun Ren, Yanhong Ji
The genes encoding the immunoglobulin κ light chain are assembled during B cell development by V(D)J recombination. For efficient rearrangement, the Igκ locus must undergo a series of epigenetic changes. One such epigenetic mark is DNA methylation. The mechanism that the Igκ locus is selectively demethylated at the pre-B cell stage has not previously been characterized. Here, we employed bisulfite DNA-modification assays to analyze the methylation status of the Igκ locus in primary pre-B cells from RAG-deficient mice with pre-rearranged Igh knock-in allele...
June 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28630088/the-islet-resident-macrophage-is-in-an-inflammatory-state-and-senses-microbial-products-in-blood
#2
Stephen T Ferris, Pavel N Zakharov, Xiaoxiao Wan, Boris Calderon, Maxim N Artyomov, Emil R Unanue, Javier A Carrero
We examined the transcriptional profiles of macrophages that reside in the islets of Langerhans of 3-wk-old non-obese diabetic (NOD), NOD.Rag1(-/-), and B6.g7 mice. Islet macrophages expressed an activation signature with high expression of Tnf, Il1b, and MHC-II at both the transcript and protein levels. These features are common with barrier macrophages of the lung and gastrointestinal tract. Moreover, injection of lipopolysaccharide induced rapid inflammatory gene expression, indicating that blood stimulants are accessible to the macrophages and that these macrophages can sense them...
June 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28630052/infection-exposure-promotes-etv6-runx1-precursor-b-cell-leukemia-via-impaired-h3k4-demethylases
#3
Guillermo Rodríguez-Hernández, Julia Hauer, Alberto Martín-Lorenzo, Daniel Schäfer, Christoph Bartenhagen, Idoia García-Ramírez, Franziska Auer, Ines Gonzalez-Herrero, Lucia Ruiz-Roca, Michael Gombert, Vera Okpanyi, Ute Fischer, Cai Chen, Martin Dugas, Sanil Bhatia, René M Linka, Marta Garcia-Suquia, María V Rascón-Trincado, Angel Garcia-Sanchez, Oscar Blanco, Maria Begona Garcia-Cenador, Francisco Javier Garcia-Criado, César Cobaleda, Diego Alonso-López, Javier De Las Rivas, Markus Müschen, Carolina Vicente-Dueñas, Isidro Sánchez-García, Arndt Borkhardt
<p>ETV6-RUNX1 is associated with the most common subtype of childhood leukemia. As few ETV6-RUNX1 carriers develop precursor B cell acute lymphocytic leukemia (pB-ALL), the underlying genetic basis for development of full-blown leukemia remains to be identified, but the appearance of leukemia cases in time-space clusters keeps infection as a potential causal factor. Here we present in vivo genetic evidence mechanistically connecting preleukemic ETV6-RUNX1 expression in hematopoetic stem cells/peripheral cells (HSC/PC) and postnatal infections for human-like pB-ALL...
June 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28629465/natural-igm-antibodies-that-bind-neoepitopes-exposed-as-a-result-of-spinal-cord-injury-drive-secondary-injury-by-activating-complement
#4
Aarti Narang, Fei Qiao, Carl Atkinson, Hong Zhu, Xiaofeng Yang, Liudmila Kulik, V Michael Holers, Stephen Tomlinson
BACKGROUND: Natural IgM antibodies (Abs) function as innate immune sensors of injury via recognition of neoepitopes expressed on damaged cells, although how this recognition systems function following spinal cord injury (SCI) exposes various neoepitopes and their precise nature remains largely unknown. Here, we investigated the role of two natural IgM monoclonal Abs (mAbs), B4 and C2, that recognize post-ischemic neoepitopes following ischemia and reperfusion in other tissues. METHODS: Identification of post-SCI expressed neoepitopes was examined using previously characterized monoclonal Abs (B4 and C2 mAbs)...
June 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28628091/the-btg2-prmt1-module-limits-pre-b-cell-expansion-by-regulating-the-cdk4-cyclin-d3-complex
#5
Elmar Dolezal, Simona Infantino, Friedel Drepper, Theresa Börsig, Aparajita Singh, Thomas Wossning, Gina J Fiala, Susana Minguet, Bettina Warscheid, David M Tarlinton, Hassan Jumaa, David Medgyesi, Michael Reth
Developing pre-B cells in the bone marrow alternate between proliferation and differentiation phases. We found that protein arginine methyl transferase 1 (PRMT1) and B cell translocation gene 2 (BTG2) are critical components of the pre-B cell differentiation program. The BTG2-PRMT1 module induced a cell-cycle arrest of pre-B cells that was accompanied by re-expression of Rag1 and Rag2 and the onset of immunoglobulin light chain gene rearrangements. We found that PRMT1 methylated cyclin-dependent kinase 4 (CDK4), thereby preventing the formation of a CDK4-Cyclin-D3 complex and cell cycle progression...
June 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28626237/cd4-t-cells-memorize-obesity-and-promote-weight-regain
#6
Jianghuan Zou, Beibei Lai, Mingzhu Zheng, Qin Chen, Shujun Jiang, Anying Song, Zan Huang, Peiliang Shi, Xin Tu, Di Wang, Linrong Lu, Zhaoyu Lin, Xiang Gao
Body weight regain often causes failure of obesity therapies while the underlying mechanism remains largely unknown. In this study, we report that immune cells, especially CD4+ T cells, mediate the 'memory' of previous obese status. In a weight gain-loss-regain model, we found that C57BL/6J mice with an obesity history showed a much faster rate of body weight regain. This obesity memory could last for at least 2 months after previously obese mice were kept at the same body weight as non-obese mice. Surprisingly, such obesity memory was abrogated by dexamethasone treatment, whereas immunodeficient Rag1(-/-) and H2A(-/-) mice failed to establish such memory...
June 19, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28620099/correction-rag1-2-induces-genomic-insertions-by-mobilizing-dna-into-rag1-2-independent-breaks
#7
Philipp C Rommel, Thiago Y Oliveira, Michel C Nussenzweig, Davide F Robbiani
No abstract text is available yet for this article.
June 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28619948/administration-of-immunobiotic-lactobacillus-plantarum-delays-but-does-not-prevent-lethal-pneumovirus-infection-in-rag1-mice
#8
Caroline M Percopo, Michelle Ma, Helene F Rosenberg
Administration of immunobiotic Lactobacillus plantarum (Lp) directly to the respiratory mucosa promotes cross-protection against lethal pneumovirus infection via B-cell-independent mechanisms. In this study, we examined Lp-mediated cross protection in Rag1(-/-) mice which cannot clear virus from lung tissue. Although Lp was initially protective, Rag1(-/-) mice ultimately succumbed to a delayed lethal outcome associated with local production of the proinflammatory cytokines CCL1, -2, and -7, granulocyte recruitment, and ongoing virus replication...
June 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28614781/cell-lines-generated-from-a-chronic-lymphocytic-leukemia-mouse-model-exhibit-constitutive-btk-and-akt-signaling
#9
Simar Pal Singh, Saravanan Y Pillai, Marjolein J W de Bruijn, Ralph Stadhouders, Odilia B J Corneth, Henk Jan van den Ham, Alice Muggen, Wilfred van IJcken, Erik Slinger, Annemieke Kuil, Marcel Spaargaren, Arnon P Kater, Anton W Langerak, Rudi W Hendriks
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature CD5+ B cells in blood. Spontaneous apoptosis of CLL cells in vitro has hampered in-depth investigation of CLL pathogenesis. Here we describe the generation of three monoclonal mouse cell lines, EMC2, EMC4 and EMC6, from the IgH.TEμ CLL mouse model based on sporadic expression of SV40 large T antigen. The cell lines exhibit a stable CD5+CD43+IgM+CD19+ CLL phenotype in culture and can be adoptively transferred into Rag1-/- mice...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588244/wandering-behaviour-prevents-inter-and-intra-oceanic-speciation-in-a-coastal-pelagic-fish
#10
Gonçalo Silva, Regina L Cunha, Ana Ramos, Rita Castilho
Small pelagic fishes have the ability to disperse over long distances and may present complex evolutionary histories. Here, Old World Anchovies (OWA) were used as a model system to understand genetic patterns and connectivity of fish between the Atlantic and Pacific basins. We surveyed 16 locations worldwide using mtDNA and 8 microsatellite loci for genetic parameters, and mtDNA (cyt b; 16S) and nuclear (RAG1; RAG2) regions for dating major lineage-splitting events within Engraulidae family. The OWA genetic divergences (0-0...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28582593/secreted-protein-acidic-and-rich-in-cysteine-functions-in-colitis-via-il17a-regulation-in-mucosal-cd4-t-cells
#11
Makoto Tanaka, Tomohisa Takagi, Yuji Naito, Kazuhiko Uchiyama, Yuma Hotta, Yuki Toyokawa, Chihiro Ushiroda, Yasuko Hirai, Wataru Aoi, Yasuki Higashimura, Katsura Mizushima, Tetsuya Okayama, Kazuhiro Katada, Kazuhiro Kamada, Takeshi Ishikawa, Osamu Handa, Yoshito Itoh
BACKGROUND AND AIM: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycol that regulates cell proliferation, tissue repair, and tumorigenesis. Despite evidence linking SPARC to inflammation, the mechanisms are unclear. Accordingly, the role of SPARC in intestinal inflammation was investigated. METHODS: Colitis was induced in wild-type (WT) and SPARC knockout (KO) mice using trinitrobenzene sulfonic acid (TNBS). Colons were assessed for damage, leukocyte infiltration, Tnf, Ifng, Il17a, and Il10 mRNA expression, and histology...
June 5, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28576128/b-cells-do-not-have-a-major-pathophysiologic-role-in-acute-ischemic-stroke-in-mice
#12
Michael K Schuhmann, Friederike Langhauser, Peter Kraft, Christoph Kleinschnitz
BACKGROUND: Lymphocytes have been shown to play an important role in the pathophysiology of acute ischemic stroke, but the properties of B cells remain controversial. The aim of this study was to unravel the role of B cells during acute cerebral ischemia using pharmacologic B cell depletion, B cell transgenic mice, and adoptive B cell transfer experiments. METHODS: Transient middle cerebral artery occlusion (60 min) was induced in wild-type mice treated with an anti-CD20 antibody 24 h before stroke onset, JHD (-/-) mice and Rag1 (-/-) mice 24 h after adoptive B cell transfer...
June 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28569776/hiv-integrase-inhibitor-elvitegravir-impairs-rag-functions-and-inhibits-v-d-j-recombination
#13
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/28566368/caspofungin-increases-fungal-chitin-and-eosinophil-and-%C3%AE-%C3%AE-t-cell-dependent-pathology-in-invasive-aspergillosis
#14
Nansalmaa Amarsaikhan, Ethan M Sands, Anand Shah, Ali Abdolrasouli, Anna Reed, James E Slaven, Darius Armstrong-James, Steven P Templeton
The polysaccharide-rich fungal cell wall provides pathogen-specific targets for antifungal therapy and distinct molecular patterns that stimulate protective or detrimental host immunity. The echinocandin antifungal caspofungin inhibits synthesis of cell wall β-1,3-glucan and is used for prophylactic therapy in immune-suppressed individuals. However, breakthrough infections with fungal pathogen Aspergillus fumigatus are associated with caspofungin prophylaxis. In this study, we report in vitro and in vivo increases in fungal surface chitin in A...
May 31, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28552805/novel-rag1-mutation-and-the-occurrence-of-mycobacterial-and-chromobacterium-violaceum-infections-in-a-case-of-leaky-scid
#15
Taj Ali Khan, Asif Iqbal, Hazir Rahman, Otavio Cabral-Marques, Muhammad Ishfaq, Noor Muhammad
Severe combined immunodeficiency (SCID) is a potentially fatal primary immunodeficiency (PID) that is caused by mutations in genes such as IL2RG, JAK3, IL7RA, RAG1, RAG2, and ADA. The products of these genes are involved in the development of several immune cells such as T, B and natural killer (NK) cells. Most of the SCID forms are autosomal recessive with the exception of IL2RG defects that cause an X-linked SCID. Among the different SCID types, there is a rare SCID form called leaky SCID, which is less severe when compared to the other classical SCID phenotypes...
May 25, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28552410/lung-eosinophil-recruitment-in-response-to-aspergillus-fumigatus-is-correlated-with-fungal-cell-wall-composition-and-requires-%C3%AE-%C3%AE-t-cells
#16
Nansalmaa Amarsaikhan, Evan M O'Dea, Angar Tsoggerel, Steven P Templeton
The differential recognition of fungal cell wall polysaccharides that program innate and adaptive immunity to the human opportunistic fungal pathogen Aspergillus fumigatus has been a focus of considerable interest. In a mouse model of fungal conidia aspiration, decreased relative levels of cell wall core carbohydrates β-1,3-glucan to chitin in A. fumigatus isolates and mutant strains were correlated with increased airway eosinophil recruitment. In addition, an increase in fungal surface chitin exposure induced by the β-1,3-glucan synthesis-targeting drug caspofungin was associated with increased murine airway eosinophil recruitment after a single challenge of conidia...
May 25, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/28550350/recent-advances-in-the-study-of-immunodeficiency-and-dna-damage-response
#17
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/28524857/a-defined-metabolic-state-in-pre-b-cells-governs-b-cell-development-and-is-counterbalanced-by-swiprosin-2-efhd1
#18
Merle Stein, Sebastian Dütting, Dimitrios Mougiakakos, Michael Bösl, Kristin Fritsch, Dorothea Reimer, Sophia Urbanczyk, Tobit Steinmetz, Wolfgang Schuh, Aline Bozec, Thomas H Winkler, Hans-Martin Jäck, Dirk Mielenz
B-cell development in the bone marrow comprises proliferative and resting phases in different niches. We asked whether B-cell metabolism relates to these changes. Compared to pro B and small pre B cells, large pre B cells revealed the highest glucose uptake and ROS but not mitochondrial mass, whereas small pre B cells exhibited the lowest mitochondrial membrane potential. Small pre B cells from Rag1(-/-);33.C9 μ heavy chain knock-in mice revealed decreased glycolysis (ECAR) and mitochondrial spare capacity compared to pro B cells from Rag1(-/-) mice...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28515359/t-cell-progenitor-therapy-facilitated-thymopoiesis-depends-upon-thymic-input-and-continued-thymic-microenvironment-interaction
#19
Michelle J Smith, Dawn K Reichenbach, Sarah L Parker, Megan J Riddle, Jason Mitchell, Kevin C Osum, Mahmood Mohtashami, Heather E Stefanski, Brian T Fife, Avinash Bhandoola, Kristin A Hogquist, Georg A Holländer, Juan Carlos Zúñiga-Pflücker, Jakub Tolar, Bruce R Blazar
Infusion of in vitro-derived T cell progenitor (proT) therapy with hematopoietic stem cell transplant aids the recovery of the thymus damaged by total body irradiation. To understand the interaction between proTs and the thymic microenvironment, WT mice were lethally irradiated and given T cell-deficient (Rag1-/-) marrow with WT in vitro-generated proTs, limiting mature T cell development to infused proTs. ProTs within the host thymus led to a significant increase in thymic epithelial cells (TECs) by day 21 after transplant, increasing actively cycling TECs...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28514688/the-e-id-protein-axis-specifies-adaptive-lymphoid-cell-identity-and-suppresses-thymic-innate-lymphoid-cell-development
#20
Masaki Miyazaki, Kazuko Miyazaki, Kenian Chen, Yi Jin, Jacob Turner, Amanda J Moore, Rintaro Saito, Kenichi Yoshida, Seishi Ogawa, Hans-Reimer Rodewald, Yin C Lin, Hiroshi Kawamoto, Cornelis Murre
Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling...
May 16, 2017: Immunity
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