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Activation induced cytidine deaminase AID

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https://www.readbyqxmd.com/read/28445143/the-igh-locus-relocalizes-to-a-recombination-compartment-in-the-perinucleolar-region-of-differentiating-b-lymphocytes
#1
Andrey Pichugin, Olga V Iarovaia, Alexey Gavrilov, Ilya Sklyar, Natalja Barinova, Aleksandr Barinov, Evgeny Ivashkin, Gersende Caron, Said Aoufouchi, Sergey V Razin, Thierry Fest, Marc Lipinski, Yegor S Vassetzky
The immunoglobulin heavy chain (IGH) gene loci are subject to specific recombination events during B-cell differentiation including somatic hypermutation and class switch recombination which mark the end of immunoglobulin gene maturation in germinal centers of secondary lymph nodes. These two events rely on the activity of activation-induced cytidine deaminase (AID) which requires DNA double strand breaks be created, a potential danger to the cell. Applying 3D-fluorescence in situ hybridization coupled with immunofluorescence staining to a previously described experimental system recapitulating normal B-cell differentiation ex vivo, we have kinetically analyzed the radial positioning of the two IGH gene loci as well as their proximity with the nucleolus, heterochromatin and γH2AX foci...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28439266/a-novel-regulator-of-activation-induced-cytidine-deaminase-apobecs-in-immunity-and-cancer-schr%C3%A3-dinger-s-catalytic-pocket
#2
REVIEW
Justin J King, Mani Larijani
Activation-induced cytidine deaminase (AID) and its relative APOBEC3 cytidine deaminases boost immune response by mutating immune or viral genes. Because of their genome-mutating activities, AID/APOBECs are also drivers of tumorigenesis. Due to highly charged surfaces, extensive non-specific protein-protein/nucleic acid interactions, formation of polydisperse oligomers, and general insolubility, structure elucidation of these proteins by X-ray crystallography and NMR has been challenging. Hence, almost all available AID/APOBEC structures are of mutated and/or truncated versions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28407558/cd11b-regulates-antibody-class-switching-via-induction-of-aid
#3
Seohyun Park, Hyunsub Sim, Hye-In Kim, Daecheol Jeong, Guang Wu, Soo Young Cho, Young Seek Lee, Hyung-Joo Kwon, Keunwook Lee
The integrin CD11b, which is encoded by the integrin subunit alpha M (ITGAM), is primarily expressed on the surface of innate immune cells. Genetic variations in ITGAM are among the strongest risk factors for systemic lupus erythematosus, an autoimmune disease characterized by the presence of autoantibodies. However, the regulatory function of CD11b in the antibody responses remains unclear. Here, we report the induction of CD11b in activated B2 B cells and define its unexpected role in immunoglobulin heavy chain class switch recombination (CSR)...
April 10, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28405512/high-expression-of-pd-1-ligands-is-associated-with-kataegis-mutational-signature-and-apobec3-alterations
#4
Amélie Boichard, Igor F Tsigelny, Razelle Kurzrock
Immunotherapy with checkpoint inhibitors, such as antibodies blocking the programmed cell-death receptor-1 (PD-1), has resulted in remarkable responses in patients having traditionally refractory cancers. Although response to PD-1 inhibitors correlates with PD-1 ligand (PD-L1 or PD-L2) expression, PD-1 ligand positivity represents only a part of the predictive model necessary for selecting patients predisposed to respond to immunotherapy. We used all genomic, transcriptomic, proteomic and phenotypic data related to 8,475 pan-cancer samples available in The Cancer Genome Atlas (TCGA) and conducted a logistic regression analysis based on a large set of variables, such as microsatellite instability (MSI-H), mismatch repair (MMR) alterations, polymerase δ (POLD1) and polymerase ε (POLE) mutations, activation-induced/apolipoprotein-B editing cytidine deaminases (AID/APOBEC) alterations, lymphocyte markers and mutation burden estimates to determine independent factors that associate with PD-1 ligand overexpression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28388279/investigation-of-aid-dicer-and-drosha-expressions-in-patients-with-chronic-lymphocytic-leukemia
#5
Metin Yusuf Gelmez, Ender Coskunpinar, Basak Saracoglu, Gunnur Deniz, Melih Aktan
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. Cytogenetic lesions such as del13q14, del11q22.3, and del17p13 are identified in 50-60% of patients. Activation-induced cytidine deaminase (AID) plays a central role in somatic hyper mutation (SHM) and class switch recombination (CSR) and functions on Ig genes, but also target non-Ig genes, and over-expression of AID can lead to point mutations or translocations in non-Ig genes such as IgH/Myc translocation. Dicer and Drosha, which have a role in activation process of miRNA, also act in a double-strand DNA break (DSB) repair mechanism...
April 7, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28346401/targeted-base-editing-in-rice-and-tomato-using-a-crispr-cas9-cytidine-deaminase-fusion
#6
Zenpei Shimatani, Sachiko Kashojiya, Mariko Takayama, Rie Terada, Takayuki Arazoe, Hisaki Ishii, Hiroshi Teramura, Tsuyoshi Yamamoto, Hiroki Komatsu, Kenji Miura, Hiroshi Ezura, Keiji Nishida, Tohru Ariizumi, Akihiko Kondo
We applied a fusion of CRISPR-Cas9 and activation-induced cytidine deaminase (Target-AID) for point mutagenesis at genomic regions specified by single guide RNAs (sgRNAs) in two crop plants. In rice, we induced multiple herbicide-resistance point mutations by multiplexed editing using herbicide selection, while in tomato we generated marker-free plants with homozygous heritable DNA substitutions, demonstrating the feasibility of base editing for crop improvement.
March 27, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28333576/epstein-barr-virus-lytic-reactivation-activates-b-cells-polyclonally-and-induces-activation-induced-cytidine-deaminase-expression-a-mechanism-underlying-autoimmunity-and-its-contribution-to-graves-disease
#7
Keiko Nagata, Keisuke Kumata, Yuji Nakayama, Yukio Satoh, Hirotsugu Sugihara, Sayuri Hara, Michiko Matsushita, Satoshi Kuwamoto, Masako Kato, Ichiro Murakami, Kazuhiko Hayashi
Graves' disease is an autoimmune disease that results in and is the most common cause of hyperthyroidism, and the reactivation of persisting Epstein-Barr virus (EBV) in B lymphocytes induces the differentiation of host B cells into plasma cells. We previously reported that some EBV-infected B cells had thyrotropin receptor antibodies (TRAbs) as surface immunoglobulins (Igs), and EBV reactivation induced these TRAb+EBV+ cells to produce TRAbs. EBV reactivation induces Ig production from host B cells. The purpose of the present study was to examine total Ig productions from B cell culture fluids and to detect activation-induced cytidine deaminase (AID), nuclear factor kappa B (NF-κB), and EBV latent membrane protein (LMP) 1 in culture B cells during EBV reactivation induction and then we discussed the mechanisms of EBV reactivation-induced Ig production in relation to autoimmunity...
April 2017: Viral Immunology
https://www.readbyqxmd.com/read/28301039/bach2-regulates-aid-mediated-immunoglobulin-gene-conversion-and-somatic-hypermutation-in-dt40-b-cells
#8
Paulina M Budzyńska, Minna K Kyläniemi, Teemu Kallonen, Anni I Soikkeli, Kalle-Pekka Nera, Olli Lassila, Jukka Alinikula
The transcription factor Bach2 is required for germinal centre formation, somatic hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulins. SHM and CSR are initiated by activation-induced cytidine deaminase (AID) which has potential to induce human B cell lymphoma. To understand the role of Bach2 in AID-mediated immunoglobulin gene diversification processes, we established a BACH2-deficient DT40 B cell line. We show that in addition to allowing SHM, Bach2 drives immunoglobulin gene conversion (GCV), another AID-dependent antibody gene diversification process...
March 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28235482/srsf1-3-contributes-to-diversification-of-the-immunoglobulin-variable-region-gene-by-promoting-accumulation-of-aid-in-the-nucleus
#9
Yuka Kawaguchi, Hiroaki Nariki, Naoko Kawamoto, Yuichi Kanehiro, Satoshi Miyazaki, Mari Suzuki, Masaki Magari, Hiroshi Tokumitsu, Naoki Kanayama
Activation-induced cytidine deaminase (AID) is essential for diversification of the Ig variable region (IgV). AID is excluded from the nucleus, where it normally functions. However, the molecular mechanisms responsible for regulating AID localization remain to be elucidated. The SR-protein splicing factor SRSF1 is a nucleocytoplasmic shuttling protein, a splicing isoform of which called SRSF1-3, has previously been shown to contribute to IgV diversification in chicken DT40 cells. In this study, we examined whether SRSF1-3 functions in IgV diversification by promoting nuclear localization of AID...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28199836/bcr-and-endosomal-tlr-signals-synergize-to-increase-aid-expression-and-establish-central-b-cell-tolerance
#10
Masayuki Kuraoka, Pilar B Snowden, Takuya Nojima, Laurent Verkoczy, Barton F Haynes, Daisuke Kitamura, Garnett Kelsoe
Activation-induced cytidine deaminase (AID) is required to purge autoreactive immature and transitional-1 (immature/T1) B cells at the first tolerance checkpoint, but how AID selectively removes self-reactive B cells is unclear. We now show that B cell antigen receptor (BCR) and endosomal Toll-like receptor (TLR) signals synergize to elicit high levels of AID expression in immature/T1 B cells. This synergy is restricted to ligands for endocytic TLR and requires phospholipase-D activation, endosomal acidification, and MyD88...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28199309/phosphatidylinositol-3-kinase-%C3%AE-blockade-increases-genomic-instability-in-b-cells
#11
Mara Compagno, Qi Wang, Chiara Pighi, Taek-Chin Cheong, Fei-Long Meng, Teresa Poggio, Leng-Siew Yeap, Elif Karaca, Rafael B Blasco, Fernanda Langellotto, Chiara Ambrogio, Claudia Voena, Adrian Wiestner, Siddha N Kasar, Jennifer R Brown, Jing Sun, Catherine J Wu, Monica Gostissa, Frederick W Alt, Roberto Chiarle
Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation...
February 23, 2017: Nature
https://www.readbyqxmd.com/read/28188246/cutting-edge-the-transcription-factor-sox2-regulates-aid-expression-in-class-switched-b-cells
#12
Lauren J DiMenna, Wei-Feng Yen, Laura Nicolas, Rahul Sharma, Zara N Saldanha, Jayanta Chaudhuri
IgH class switch recombination (CSR) occurs through the deliberate introduction of activation-induced cytidine deaminase (AID)-instigated DNA double-strand breaks into the IgH loci. Because double-strand breaks are generally highly toxic, mechanisms that regulate AID expression are of much relevance to CSR and genomic integrity; however, effectors of such regulatory processes are still poorly understood. In this article, we show that the transcription factor sex determining region Y-box 2 (Sox2) is expressed in activated B cells, but almost exclusively in those that have undergone CSR...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28154564/immunization-of-newborn-mice-accelerates-the-architectural-maturation-of-lymph-nodes-but-aid-dependent-igg-responses-are-still-delayed-compared-to-the-adult
#13
Rosario Munguía-Fuentes, Juan Carlos Yam-Puc, Aarón Silva-Sánchez, Edith Marcial-Juárez, Isis Amara Gallegos-Hernández, Juana Calderón-Amador, Troy D Randall, Leopoldo Flores-Romo
Lymph nodes (LNs) have evolved to maximize antigen (Ag) collection and presentation as well as lymphocyte proliferation and differentiation-processes that are spatially regulated by stromal cell subsets, including fibroblastic reticular cells (FRCs) and follicular dendritic cells (FDCs). Here, we showed that naïve neonatal mice have poorly organized LNs with few B and T cells and undetectable FDCs, whereas adult LNs have numerous B cells and large FDC networks. Interestingly, immunization on the day of birth accelerated B cell accumulation and T cell recruitment into follicles as well as FDC maturation and FRC organization in neonatal LNs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28147265/gender-differences-in-global-but-not-targeted-demethylation-in-ipsc-reprogramming
#14
Inês Milagre, Thomas M Stubbs, Michelle R King, Julia Spindel, Fátima Santos, Felix Krueger, Martin Bachman, Anne Segonds-Pichon, Shankar Balasubramanian, Simon R Andrews, Wendy Dean, Wolf Reik
Global DNA demethylation is an integral part of reprogramming processes in vivo and in vitro, but whether it occurs in the derivation of induced pluripotent stem cells (iPSCs) is not known. Here, we show that iPSC reprogramming involves both global and targeted demethylation, which are separable mechanistically and by their biological outcomes. Cells at intermediate-late stages of reprogramming undergo transient genome-wide demethylation, which is more pronounced in female cells. Global demethylation requires activation-induced cytidine deaminase (AID)-mediated downregulation of UHRF1 protein, and abolishing demethylation leaves thousands of hypermethylated regions in the iPSC genome...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28140712/the-clinical-characteristics-and-prognostic-significance-of-aid-mir-181b-and-mir-155-expression-in-adult-patients-with-de-novo-b-cell-acute-lymphoblastic-leukemia
#15
Guangquan Zhou, Yang Cao, Weimin Dong, Yan Lin, Qi Wang, Wei Wu, Xiaoying Hua, Yun Ling, Xiaobao Xie, Shaoyan Hu, Jiannong Cen, Weiying Gu
This study aimed to investigate clinical characteristics and prognostic significance of activation-induced cytidine deaminase (AID) gene, miR-181b and miR-155 expression in de novo adult B-cell acute lymphoblastic leukemia (B-ALL) patients. Results showed that AID and miR-155 expression were higher in B-ALL patients than healthy controls, while miR-181b expression was lower in B-ALL patients. In addition, Ph(+) B-ALLs had higher AID expression than Ph(-) B-ALLs, and its high expression was associated with BCR-ABL...
January 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28088785/the-igh-locus-3-cis-regulatory-super-enhancer-co-opts-aid-for-allelic-transvection
#16
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...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077417/aid-is-a-key-regulator-of-myeloid-erythroid-differentiation-and-dna-methylation-in-hematopoietic-stem-progenitor-cells
#17
Hiroyoshi Kunimoto, Anna Sophia McKenney, Cem Meydan, Kaitlyn Shank, Abbas Nazir, Franck Rapaport, Benjamin Durham, Francine E Garrett-Bakelman, Elodie Pronier, Alan H Shih, Ari Melnick, Jayanta Chaudhuri, Ross L Levine
Recent studies have reported that activation-induced cytidine deaminase (AID) and ten-eleven-translocation (TET) family members regulate active DNA demethylation. Genetic alterations of TET2 occur in myeloid malignancies, and hematopoietic-specific loss of Tet2 induces aberrant hematopoietic stem cell (HSC) self-renewal/differentiation, implicating TET2 as a master regulator of normal and malignant hematopoiesis. Despite the functional link between AID and TET in epigenetic gene regulation, the role of AID loss in hematopoiesis and myeloid transformation remains to be investigated...
March 30, 2017: Blood
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
#18
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
#19
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 7, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28063995/activation-of-tnf-%C3%AE-aid-axis-and-co-inhibitory-signals-in-coordination-with-th1-type-immunity-in-a-mouse-model-recapitulating-hepatitis-b
#20
Tomonori Matsumoto, Ken Takahashi, Tadashi Inuzuka, Soo Ki Kim, Tomoaki Kurosaki, Shigeru Kawakami, Tsutomu Chiba, Hiroshi Seno, Hiroyuki Marusawa
Hepatitis B virus (HBV) infection evokes host immune responses that primarily determine the outcome of HBV infection and the clinical features of HBV-associated liver disease. The precise mechanisms by which host factors restrict HBV replication, however, are poorly understood due to the lack of useful animal models that recapitulate immune responses to HBV. Here, we performed comprehensive immunologic gene expression profiling of the liver of a mouse model recapitulating anti-HBV immune response using a high sensitivity direct digital counting system...
January 5, 2017: Antiviral Research
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