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Class switch recombination

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https://www.readbyqxmd.com/read/28088785/the-igh-locus-3-cis-regulatory-super-enhancer-co-opts-aid-for-allelic-transvection
#1
Sandrine Le Noir, Brice Laffleur, Claire Carrion, Armand Garot, Sandrine Lecardeur, Eric Pinaud, Yves Denizot, Jane Skok, Michel Cogné
Immunoglobulin heavy chain (IgH) alleles have ambivalent relationships: they feature both allelic exclusion, ensuring monoallelic expression of a single immunoglobulin (Ig) allele, and frequent inter-allelic class-switch recombination (CSR) reassembling genes from both alleles. The IgH locus 3' regulatory region (3'RR) includes several transcriptional cis-enhancers promoting activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (SHM) and CSR, and altogether behaves as a strong super-enhancer...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28073404/isolation-and-characterization-of-hiv-1-envelope-glycoprotein-specific-b-cell-from-immortalized-human-na%C3%A3-ve-b-cell-library
#2
Zehua Sun, Shiqiang Lu, Zheng Yang, Jingjing Li, Meiyun Zhang
With the recent development of single B cell cloning techniques, an increasing number of HIV-1-specific broadly neutralizing antibodies (bNAbs) have been isolated since 2009. However, knowledge regarding HIV-1-specific B cells in vivo is limited. In this study, an HIV-1-specific B cell line has been established using healthy PBMC donors by the highly efficient EBV transformation method to generate immortalized human naïve B cell libraries. The enrichment of HIV-1 envelope-specific B cells was observed after four rounds of cell panning with the HIV-1 envelope glycoprotein...
January 10, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28069372/rna-exosome-and-non-coding-rna-coupled-mechanisms-in-aid-mediated-genomic-alterations
#3
REVIEW
Brice Laffleur, Uttiya Basu, Junghyun Lim
The eukaryotic RNA exosome is a well-conserved protein complex with ribonuclease activity implicated in RNA metabolism. Various families of non-coding RNAs have been identified as substrates of the complex, underscoring its role as a non-coding RNA processing/degradation unit. However, the role of RNA exosome and its RNA processing activity on DNA mutagenesis/alteration events have not been investigated until recently. B lymphocytes use two DNA alteration mechanisms, class switch recombination (CSR) and somatic hypermutation (SHM), to re-engineer their antibody gene expressing loci until a tailored antibody gene for a specific antigen is satisfactorily generated...
January 6, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28065739/r-loop-depletion-by-over-expressed-rnase-h1-in-mouse-b-cells-increases-activation-induced-deaminase-access-to-the-transcribed-strand-without-altering-frequency-of-isotype-switching
#4
Robert W Maul, Hyongi Chon, Kiran Sakhuja, Susana M Cerritelli, Lina A Gugliotti, Patricia J Gearhart, Robert J Crouch
R-loops, three-strand structures consisting of mRNA hybridized to the complementary DNA and a single-stranded DNA loop, are formed in switch regions on the heavy-chain immunoglobulin locus. To determine if R-loops have a direct effect on any of the steps involved in isotype switching, we generated a transgenic mouse that over-expressed RNase H1, an enzyme that cleaves the RNA of RNA/DNA hybrids in B cells. R-loops in the switch μ region were depleted by 70% in ex vivo activated splenic B cells. Frequencies of isotype switching to IgG1, IgG2b, IgG2c, and IgG3 were the same as C57BL/6 control cells...
January 6, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28058717/deletional-tolerance-prevents-aqp4-directed-autoimmunity-in-mice
#5
Anna-Lena Vogel, Benjamin Knier, Katja Lammens, Sudhakar Reddy Kalluri, Tanja Kuhlmann, Jeffrey L Bennett, Thomas Korn
Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system (CNS) mediated by antibodies to water channel protein AQP4 expressed in astrocytes. The contribution of AQP4-specific T cells to the class switch recombination of pathogenic AQP4-specific antibodies and to the inflammation of the blood-brain-barrier is incompletely understood, as immunogenic naturally processed T-cell epitopes of AQP4 are unknown. By immunizing Aqp4(-/-) mice with full length murine AQP4 protein followed by recall with overlapping peptides, we here identify AQP4(201-220) as the major immunogenic IA(b) -restricted epitope of AQP4...
January 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28012163/il-10-production-in-murine-igm-cd138-hi-cells-is-driven-by-blimp1-and-downregulated-in-class-switched-cells
#6
Nao Suzuki-Yamazaki, Rieko Yanobu-Takanashi, Tadashi Okamura, Satoshi Takaki
In contrast to antibody-induced inflammatory responses, some B-cell subpopulations suppress inflammation through the production of interleukin (IL)-10. However, the mechanisms underlying Il10 gene expression during B-cell development is elusive. Here, we identify IgM(+) B220(lo) CD138(hi) cells responsible for marked IL-10 production in the bone marrow and spleen of mice. These murine IL-10-producing cells predominantly secrete IgM and have unique characteristics of long-lived plasma cells in spite of high expression of surface IgM...
December 23, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/28011866/the-aryl-hydrocarbon-receptor-controls-cell-fate-decisions-in-b-cells
#7
Bharat Vaidyanathan, Ashutosh Chaudhry, William T Yewdell, Davide Angeletti, Wei-Feng Yen, Adam K Wheatley, Christopher A Bradfield, Adrian B McDermott, Jonathan W Yewdell, Alexander Y Rudensky, Jayanta Chaudhuri
Generation of cellular heterogeneity is an essential feature of the adaptive immune system. This is best exemplified during humoral immune response when an expanding B cell clone assumes multiple cell fates, including class-switched B cells, antibody-secreting plasma cells, and memory B cells. Although each cell type is essential for immunity, their generation must be exquisitely controlled because a class-switched B cell cannot revert back to the parent isotype, and a terminally differentiated plasma cell cannot contribute to the memory pool...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28000955/chronic-airway-inflammation-provides-a-unique-environment-for-b-cell-activation-and-antibody-production
#8
Scott Feldman, Richard Kasjanski, Julie Popowski, David Hernandez, Jason Chen, James E Norton, Lydia Suh, Roderick G Carter, Whitney W Stevens, Anju T Peters, Robert C Kern, David B Conley, Bruce K Tan, Stephani Shintani-Smith, Kevin C Welch, Leslie C Grammer, Kathleen E Harris, Atsushi Kato, Robert P Schleimer, Kathryn E Hulse
BACKGROUND: B cells play many roles in health and disease. However, little is known about the mechanisms that drive B cell responses in the airways, especially in humans. Chronic rhinosinusitis (CRS) is an inflammatory disease of the upper airways that affects 10% of Europeans and Americans. A subset of CRS patients develop nasal polyps (NP), which are characterized by type 2 inflammation, eosinophils and group 2 innate lymphoid cells (ILC2). We have reported that NP contain elevated levels of B cells and antibodies, making NP an ideal system for studying B cells in the airways...
December 21, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27998928/the-cell-cycle-restricts-activation-induced-cytidine-deaminase-activity-to-early-g1
#9
Qiao Wang, Kyong-Rim Kieffer-Kwon, Thiago Y Oliveira, Christian T Mayer, Kaihui Yao, Joy Pai, Zhen Cao, Marei Dose, Rafael Casellas, Mila Jankovic, Michel C Nussenzweig, Davide F Robbiani
Activation-induced cytidine deaminase (AID) converts cytosine into uracil to initiate somatic hypermutation (SHM) and class switch recombination (CSR) of antibody genes. In addition, this enzyme produces DNA lesions at off-target sites that lead to mutations and chromosome translocations. However, AID is mostly cytoplasmic, and how and exactly when it accesses nuclear DNA remains enigmatic. Here, we show that AID is transiently in spatial contact with genomic DNA from the time the nuclear membrane breaks down in prometaphase until early G1, when it is actively exported into the cytoplasm...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27997339/toll-like-receptor-3-adjuvant-in-combination-with-virus-like-particles-elicit-a-humoral-response-against-hiv
#10
Ethan Poteet, Phoebe Lewis, Changyi Chen, Sam On Ho, Thai Do, SuMing Chiang, Celia Labranche, David Montefiori, Gary Fujii, Qizhi Yao
Human Immunodeficiency Virus (HIV) Virus-Like Particles (VLPs) composed of HIVIIIB Gag and HIVBaL gp120/gp41 envelope are a pseudovirion vaccine capable of presenting antigens in their native conformations. To enhance the immunogenicity of the HIV Env antigen, VLPs were coupled to VesiVax Conjugatable Adjuvant Lipid Vesicles (CALV) containing one of four toll-like-receptor (TLR) ligands, each activating a receptor with distinct cellular localization and downstream pathways. C57BL/6 mice were vaccinated by intranasal prime followed by two sub-cheek boosts and their sera immunoglobulin and neutralizing potency were measured over a duration of 3months after vaccination...
November 21, 2016: Vaccine
https://www.readbyqxmd.com/read/27974461/the-gs-protein-coupled-a2a-adenosine-receptor-controls-t-cell-help-in-the-germinal-center
#11
Robert K Abbott, Murillo Silva, Jasmine Labuda, Molly Thayer, Derek W Cain, Phaethon Philbrook, Shalini Sethumadhavan, Stephen Hatfield, Akio Ohta, Michail Sitkovsky
T follicular helper (TFH) cells have been shown to be critically required for the germinal center (GC) reaction where B cells undergo class switch recombination and clonal selection to generate high affinity neutralizing antibodies. However, detailed knowledge of the physiological cues within the GC microenvironment that regulate T cell help is limited. The cAMP elevating, Gs protein coupled A2a adenosine receptor (A2aR) is an evolutionarily conserved receptor that limits and redirects cellular immunity. However, the role of A2aR in humoral immunity and B cell differentiation is unknown...
December 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27974207/dna-replication-origins-in-immunoglobulin-switch-regions-regulate-class-switch-recombination-in-an-r-loop-dependent-manner
#12
Eva-Maria Wiedemann, Mihaela Peycheva, Rushad Pavri
Class switch recombination (CSR) at the immunoglobulin heavy chain (IgH) locus generates antibody isotypes. CSR depends on double-strand breaks (DSBs) induced by activation-induced cytidine deaminase (AID). Although DSB formation and repair machineries are active in G1 phase, efficient CSR is dependent on cell proliferation and S phase entry; however, the underlying mechanisms are obscure. Here, we show that efficient CSR requires the replicative helicase, the Mcm complex. Mcm proteins are enriched at IgH switch regions during CSR, leading to assembly of facultative replication origins that require Mcm helicase function for productive CSR...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27931848/human-peripheral-late-exhausted-memory-b-cells-express-a-senescent-associated-secretory-phenotype-and-preferentially-utilize-metabolic-signaling-pathways
#13
Daniela Frasca, Alain Diaz, Maria Romero, Bonnie B Blomberg
The percentage of late/exhausted memory (LM) B cells increases with age and we show here that this is associated with a lower influenza vaccine response. To identify novel contributors to the phenotypic and functional changes observed in aged B cells, we sorted the major peripheral B cell subsets [naïve, IgM memory, switched memory (swIg) and late/exhausted memory (LM)] and determined their percentages in the peripheral blood as well as their level of immune activation by measuring basal levels of expression of multiple senescence-associated secretory phenotype (SASP) markers, such as pro-inflammatory cytokines (TNF-α/IL-6/IL-8), inflammatory micro-RNAs (miRs, miR-155/16/93), cell cycle regulators (p16(INK4))...
January 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/27925349/hepatitis-c-viraemia-reversibly-maintains-subset-of-antigen-specific-t-bet-tissue-like-memory-b-cells
#14
L-Y Chang, Y Li, D E Kaplan
BACKGROUND: Chronic antigen exposure and/or ageing increases the frequency of T-box expressed in T cells (T-bet)-expressing B-lymphocytes in mice. The frequency and significance of B-cell T-bet expression during chronic hepatitis C (HCV) infection in human subjects has never been described. METHODS: Healthy controls, cirrhotic and noncirrhotic HCV-infected patients, and non-HCV patients with cirrhosis were recruited. Peripheral blood mononuclear cells were phenotyped for expression of T-bet and related markers by flow cytometry...
December 7, 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/27924011/roles-for-aprin-pds5b-in-homologous-recombination-and-in-ovarian-cancer-prediction
#15
Anthony M Couturier, Hubert Fleury, Anne-Marie Patenaude, Victoria L Bentley, Amélie Rodrigue, Yan Coulombe, Joshi Niraj, Joris Pauty, Jason N Berman, Graham Dellaire, Javier M Di Noia, Anne-Marie Mes-Masson, Jean-Yves Masson
APRIN (PDS5 cohesin associated factor B) interacts with both the cohesin complex and the BRCA2 tumor suppressor. How APRIN influences cohesion and DNA repair processes is not well understood. Here, we show that APRIN is recruited to DNA damage sites. We find that APRIN interacts directly with RAD51, PALB2 and BRCA2. APRIN stimulates RAD51-mediated DNA strand invasion. APRIN also binds DNA with an affinity for D-loop structures and single-strand (ss) DNA. APRIN is a new homologous recombination (HR) mediator as it counteracts the RPA inhibitory effect on RAD51 loading to ssDNA...
December 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27897229/global-gene-regulation-during-activation-of-immunoglobulin-class-switching-in-human-b-cells
#16
Youming Zhang, David J Fear, Saffron A G Willis-Owen, William O Cookson, Miriam F Moffatt
Immunoglobulin class switch recombination (CSR) to IgE is a tightly regulated process central to atopic disease. To profile the B-cell transcriptional responses underlying the activation of the germinal centre activities leading to the generation of IgE, naïve human B-cells were stimulated with IL-4 and anti-CD40. Gene expression and alternative splicing were profiled over 12 days using the Affymetrix Human Exon 1.0 ST Array. A total of 1,399 genes, forming 13 temporal profiles were differentially expressed...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27890643/coordination-of-dna-single-strand-break-repair
#17
Rachel Abbotts, David M Wilson
The genetic material of all organisms is susceptible to modification. In some instances, these changes are programmed, such as the formation of DNA double strand breaks during meiotic recombination to generate gamete variety or class switch recombination to create antibody diversity. However, in most cases, genomic damage is potentially harmful to the health of the organism, contributing to disease and aging by promoting deleterious cellular outcomes. A proportion of DNA modifications are caused by exogenous agents, both physical (namely ultraviolet sunlight and ionizing radiation) and chemical (such as benzopyrene, alkylating agents, platinum compounds and psoralens), which can produce numerous forms of DNA damage, including a range of "simple" and helix-distorting base lesions, abasic sites, crosslinks and various types of phosphodiester strand breaks...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27871841/rubber-particle-proteins-ref1-and-srpp1-interact-differently-with-native-lipids-extracted-from-hevea-brasiliensis-latex
#18
Kanthida Wadeesirisak, Sabine Castano, Karine Berthelot, Laurent Vaysse, Frédéric Bonfils, Frédéric Peruch, Kittipong Rattanaporn, Siriluck Liengprayoon, Sophie Lecomte, Céline Bottier
Rubber particle membranes from the Hevea latex contain predominantly two proteins, REF1 and SRPP1 involved in poly(cis-1,4-isoprene) synthesis or rubber quality. The repartition of both proteins on the small or large rubber particles seems to differ, but their role in the irreversible coagulation of the rubber particle is still unknown. In this study we highlighted the different modes of interactions of both recombinant proteins with different classes of lipids extracted from Hevea brasiliensis latex, and defined as phospholipids (PL), glycolipids (GL) and neutral lipids (NL)...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27853268/kin17-facilitates-multiple-double-strand-break-repair-pathways-that-govern-b-cell-class-switching
#19
Michael X Le, Dania Haddad, Alexanda K Ling, Conglei Li, Clare C So, Amit Chopra, Rui Hu, Jaime F Angulo, Jason Moffat, Alberto Martin
Class switch recombination (CSR) in B cells requires the timely repair of DNA double-stranded breaks (DSBs) that result from lesions produced by activation-induced cytidine deaminase (AID). Through a genome-wide RNAi screen, we identified Kin17 as a gene potentially involved in the maintenance of CSR in murine B cells. In this study, we confirm a critical role for Kin17 in CSR independent of AID activity. Furthermore, we make evident that DSBs generated by AID or ionizing radiation require Kin17 for efficient repair and resolution...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27837104/cutting-edge-baff-overexpression-reduces-atherosclerosis-via-taci-dependent-b-cell-activation
#20
Shaun W Jackson, Nicole E Scharping, Holly M Jacobs, Shari Wang, Alan Chait, David J Rawlings
Patients with systemic lupus erythematosus exhibit accelerated atherosclerosis, a chronic inflammatory disease of the arterial wall. The impact of B cells in atherosclerosis is controversial, with both protective and pathogenic roles described. For example, natural IgM binding conserved oxidized lipid epitopes protect against atherosclerosis, whereas anti-oxidized low-density lipoprotein (oxLDL) IgG likely promotes disease. Because BAFF promotes B cell class-switch recombination and humoral autoimmunity, we hypothesized that excess BAFF would accelerate atherosclerosis...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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