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Activation induced cytidine deaminase AID

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https://www.readbyqxmd.com/read/29427373/advanced-cirrhosis-drives-enhanced-b-cell-differentiation-resulting-in-hyperglobulinemia
#1
Hiroyoshi Doi, Eiichi Hayashi, Jun Arai, Masayuki Tojo, Kenichi Morikawa, Junichi Eguchi, Takayoshi Ito, Tatsuya Kanto, David E Kaplan, Hitoshi Yoshida
BACKGROUND AND AIM: The mechanism underlying hyperglobulinemia in cirrhosis, a long appreciated phenomenon, has never been clearly understood. The aim of this study is to investigate the basis for changes in humoral immunity observed in cirrhosis. METHODS: We retrospectively reviewed our medical record to analyze serum immunoglobulin levels in patients with liver disease. We also prospectively analyzed peripheral blood mononuclear cells (PBMC) and sera from liver disease patients...
February 10, 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29388096/activation-induced-cytidine-deaminase-aided-in-vitro-antibody-evolution
#2
Lili An, Chuan Chen, Ruiqi Luo, Yun Zhao, Haiying Hang
Activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) by converting deoxycytidines (dC) to deoxyuracils (dU) which then can induce other mutations, and plays a central role in introducing diversification of the antibody repertoire in B cells. Ectopic expression of AID in bacteria and non-B cells can also lead to frequent mutations in highly expressed genes. Taking advantage of this feature of AID, in recent years, systems coupling in vitro somatic hypermutation and mammalian cell surface display have been developed, with unique benefits in antibody discovery and optimization in vitro...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29343743/expression-and-subcellular-localisation-of-aid-and-apobec3-in-adenoid-and-palatine-tonsils
#3
Noriko Seishima, Satoru Kondo, Kousho Wakae, Naohiro Wakisaka, Eiji Kobayashi, Makoto Kano, Makiko Moriyama-Kita, Yosuke Nakanishi, Kazuhira Endo, Tomoko Imoto, Kazuya Ishikawa, Hisashi Sugimoto, Miyako Hatano, Takayoshi Ueno, Miki Koura, Koichi Kitamura, Masamichi Muramatsu, Tomokazu Yoshizaki
Activation-induced cytidine deaminase (AID) and apolipoprotein B mRNA-editing catalytic polypeptide 3 (A3) family are cytidine deaminases that play critical roles in B-cell maturation, antiviral immunity and carcinogenesis. Adenoids and palatine tonsils are secondary lymphoid immune organs, in which AID and A3s are thought to have several physiological or pathological roles. However, the expression of AID or A3s in these organs has not been investigated. Therefore, we investigated the expression profiles of AID and A3s, using 67 samples of adenoids and palatine tonsils from patients, with reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical analyses...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321370/activation-induced-cytidine-deaminase-deficiency-accelerates-autoimmune-diabetes-in-nod-mice
#4
Qiyuan Tan, Ningwen Tai, Yangyang Li, James Pearson, Sean Pennetti, Zhiguang Zhou, F Susan Wong, Li Wen
B cells play an important role in type 1 diabetes (T1D) development. However, the role of B cell activation-induced cytidine deaminase (AID) in diabetes development is not clear. We hypothesized that AID is important in the immunopathogenesis of T1D. To test this hypothesis, we generated AID-deficient (AID-/-) NOD mice. We found that AID-/-NOD mice developed accelerated T1D, with worse insulitis and high levels of anti-insulin autoantibody in the circulation. Interestingly, neither maternal IgG transferred through placenta, nor IgA transferred through milk affected the accelerated diabetes development...
January 11, 2018: JCI Insight
https://www.readbyqxmd.com/read/29251015/prognostic-impact-of-activation-induced-cytidine-deaminase-expression-for-patients-with-diffuse-large-b-cell-lymphoma
#5
Hiroshi Arima, Masakazu Fujimoto, Momoko Nishikori, Toshiyuki Kitano, Wataru Kishimoto, Masakatsu Hishizawa, Tadakazu Kondo, Kouhei Yamashita, Masahiro Hirata, Hironori Haga, Akifumi Takaori-Kondo
Activation-induced cytidine deaminase (AID) plays important roles in the development of diffuse large B-cell lymphoma (DLBCL); however, its prognostic value remains controversial. Here, we evaluated AID expression in 71 DLBCL patients treated with R-CHOP by immunohistochemistry and investigated its prognostic significance. AID expression was detected in 40.8% of DLBCL samples and associated with IRF4 expression. Notably, AID expression correlated with shorter progression-free survival and overall survival for patients with high (3-5) international prognostic index (IPI) score...
December 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29199976/hydrogen-bonds-are-a-primary-driving-force-for-de-novo-protein-folding
#6
Schuyler Lee, Chao Wang, Haolin Liu, Jian Xiong, Renee Jiji, Xia Hong, Xiaoxue Yan, Zhangguo Chen, Michal Hammel, Yang Wang, Shaodong Dai, Jing Wang, Chengyu Jiang, Gongyi Zhang
The protein-folding mechanism remains a major puzzle in life science. Purified soluble activation-induced cytidine deaminase (AID) is one of the most difficult proteins to obtain. Starting from inclusion bodies containing a C-terminally truncated version of AID (residues 1-153; AID153), an optimized in vitro folding procedure was derived to obtain large amounts of AID153, which led to crystals with good quality and to final structural determination. Interestingly, it was found that the final refolding yield of the protein is proline residue-dependent...
December 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/29188055/aberrant-expression-of-interleukin-10-and-activation-induced-cytidine-deaminase-in-b-cells-from-patients-with-beh%C3%A3-et-s-disease
#7
Jeong-Yun Yoon, Yeojin Lee, Seong-Lan Yu, Hee-Kyung Yoon, Ha-Yan Park, Chung-Il Joung, Seok-Rae Park, Mihye Kwon, Jaeku Kang
Despite extensive studies, the pathogenesis of Behçet's disease (BD) remains unclear. In particular, the roles of B cells in patients with BD have not been elucidated. Activation-induced cytidine deaminase (AID) is a critical enzyme for immunoglobulin (Ig) heavy chain class switching and somatic hypermutation in B cells and the abnormal expression of AID in various immune conditions has previously been studied. B10 cells, an interleukin (IL)-10-secreting subset of regulatory B cells, function to downregulate inflammation and autoimmunity...
December 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29161581/dna-rna-hybrid-substrates-modulate-the-catalytic-activity-of-purified-aid
#8
COMPARATIVE STUDY
Hala S Abdouni, Justin J King, Atefeh Ghorbani, Heather Fifield, Lesley Berghuis, Mani Larijani
Activation-induced cytidine deaminase (AID) converts cytidine to uridine at Immunoglobulin (Ig) loci, initiating somatic hypermutation and class switching of antibodies. In vitro, AID acts on single stranded DNA (ssDNA), but neither double-stranded DNA (dsDNA) oligonucleotides nor RNA, and it is believed that transcription is the in vivo generator of ssDNA targeted by AID. It is also known that the Ig loci, particularly the switch (S) regions targeted by AID are rich in transcription-generated DNA/RNA hybrids...
January 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29158395/histone-methyltransferase-mmset-promotes-aid-mediated-dna-breaks-at-the-donor-switch-region-during-class-switch-recombination
#9
Hai Vu Nguyen, Junchao Dong, Rohit A Panchakshari, Vipul Kumar, Frederick W Alt, Jean-Christophe Bories
In B cells, Ig class switch recombination (CSR) is initiated by activation-induced cytidine deaminase (AID), the activity of which leads to DNA double-strand breaks (DSBs) within IgH switch (S) regions. Preferential targeting of AID-mediated DSBs to S sequences is critical for allowing diversification of antibody functions, while minimizing potential off-target oncogenic events. Here, we used gene targeted inactivation of histone methyltransferase (HMT) multiple myeloma SET domain (MMSET) in mouse B cells and the CH12F3 cell line to explore its role in CSR...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29136157/depletion-of-recombination-specific-co-factors-by-the-c-terminal-mutant-of-the-activation-induced-cytidine-deaminase-causes-the-dominant-negative-effect-on-class-switch-recombination
#10
Azza Al Ismail, Afzal Husain, Maki Kobayashi, Tasuku Honjo, Nasim A Begum
Activation-induced cytidine deaminase (AID) is essential for class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin (Ig) genes. Studies on in vitro mutagenized AID as well as its mutations in human patients with Hyper-IgM (HIGM)-syndrome type II revealed that C-terminal AID mutations were defective in CSR whereas their DNA cleavage and SHM activities remained intact. The C-terminal mutants of AID were speculated to exert the dominant negative effect on wild type WT AID whereas its mechanism remains unknown...
November 10, 2017: International Immunology
https://www.readbyqxmd.com/read/29122947/phosphorylation-promotes-activation-induced-cytidine-deaminase-activity-at-the-myc-oncogene
#11
Yunxiang Mu, Monika A Zelazowska, Kevin M McBride
Activation-induced cytidine deaminase (AID) is a mutator enzyme that targets immunoglobulin (Ig) genes to initiate antibody somatic hypermutation (SHM) and class switch recombination (CSR). Off-target AID association also occurs, which causes oncogenic mutations and chromosome rearrangements. However, AID occupancy does not directly correlate with DNA damage, suggesting that factors beyond AID association contribute to mutation targeting. CSR and SHM are regulated by phosphorylation on AID serine38 (pS38), but the role of pS38 in off-target activity has not been evaluated...
December 4, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29100269/activation-induced-cytidine-deaminase-prevents-pro-b-cell-acute-lymphoblastic-leukemia-by-functioning-as-a-negative-regulator-in-rag1-deficient-pro-b-cells
#12
Franziska Auer, Deborah Ingenhag, Stefan Pinkert, Sven Kracker, Salima Hacein-Bey-Abina, Marina Cavazzana, Michael Gombert, Alberto Martin-Lorenzo, Min-Hui Lin, Carolina Vicente-Dueñas, Isidro Sánchez-García, Arndt Borkhardt, Julia Hauer
Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation and class switch recombination in mature B-cells, while AID was also shown to play a role in developing pre-BCR/BCR-positive B-cells of the bone marrow. To further elucidate a potential function of Aid in the bone marrow prior to V(D)J-recombination, we utilized an in vivo model which exerts a B-cell developmental arrest at the pro-B cell stage with low frequencies of pro-B cell acute lymphoblastic leukemia (pro-B ALL) development...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29070849/high-risk-follicular-lymphomas-harbour-more-somatic-mutations-including-those-in-the-aid-motif
#13
Taku Tsukamoto, Masakazu Nakano, Ryuichi Sato, Hiroko Adachi, Miki Kiyota, Eri Kawata, Nobuhiko Uoshima, Satoru Yasukawa, Yoshiaki Chinen, Shinsuke Mizutani, Yuji Shimura, Tsutomu Kobayashi, Shigeo Horiike, Akio Yanagisawa, Masafumi Taniwaki, Kei Tashiro, Junya Kuroda
We investigated clinical and genetic characteristics of high-risk follicular lymphoma (FL), that lacked evidence of large cell transformation at diagnosis, in the rituximab era. First, we retrospectively analysed the clinical features of 100 patients with non-transformed FL that were consecutively treated with rituximab-containing therapies in a discovery cohort. The presence of either peripheral blood and/or bone involvement was associated with short progression-free survival. This was confirmed in a validation cohort of 66 FL patients...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28973905/physical-proximity-of-chromatin-to-nuclear-pores-prevents-harmful-r-loop-accumulation-contributing-to-maintain-genome-stability
#14
Francisco García-Benítez, Hélène Gaillard, Andrés Aguilera
During transcription, the mRNA may hybridize with DNA, forming an R loop, which can be physiological or pathological, constituting in this case a source of genomic instability. To understand the mechanism by which eukaryotic cells prevent harmful R loops, we used human activation-induced cytidine deaminase (AID) to identify genes preventing R loops. A screening of 400 Saccharomyces cerevisiae selected strains deleted in nuclear genes revealed that cells lacking the Mlp1/2 nuclear basket proteins show AID-dependent genomic instability and replication defects that were suppressed by RNase H1 overexpression...
October 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28972092/ship-1-deficiency-in-aid-b-cells-leads-to-the-impaired-function-of-b10-cells-with-spontaneous-autoimmunity
#15
Yingjia Chen, Fanlei Hu, Xuejiao Dong, Meng Zhao, Jing Wang, Xiaolin Sun, Tae Jin Kim, Zhanguo Li, Wanli Liu
Unlike conventional B cells, regulatory B cells exhibit immunosuppressive functions to downregulate inflammation via IL-10 production. However, the molecular mechanism regulating the production of IL-10 is not fully understood. In this study, we report the finding that activation-induced cytidine deaminase (AID) is highly upregulated in the IL-10-competent B cell (B10) cell from Innp5d(fl/fl)Aicda(Cre/+) mice, whereas the 5' inositol phosphatase SHIP-1 is downregulated. Notably, SHIP-1 deficiency in AID(+) B cells leads to a reduction in cell count and impaired IL-10 production by B10 cells...
November 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28959900/expression-of-activation-induced-cytidine-deaminase-splicing-variants-in-patients-with-ankylosing-spondylitis
#16
Ji-Young Kim, Hee-Kyung Yoon, Seung Taek Song, Seok-Rae Park, Seung-Cheol Shim
To investigate the expression patterns of activation-induced cytidine deaminase (AID) variants in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and examine their clinical implications, we isolated PBMCs from healthy controls (HC, n = 33) and patients with AS (n = 62), and measured mRNA expression of AID variants and translesion synthesis (TLS) polymerases using quantitative real-time polymerase chain reaction. The proportion of patients with AS in whom AID splicing variant (sv) 2 was expressed was significantly higher than that of HC (p = ...
September 29, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28959124/higher-expression-of-activation-induced-cytidine-deaminase-is-significantly-associated-with-merkel-cell-polyomavirus-negative-merkel-cell-carcinomas
#17
Michiko Matsushita, Takeshi Iwasaki, Daisuke Nonaka, Satoshi Kuwamoto, Keiko Nagata, Masako Kato, Yukisato Kitamura, Kazuhiko Hayashi
BACKGROUND: Merkel cell carcinomas (MCCs), clinically aggressive neuroendocrine skin cancers, are divided into Merkel cell polyomavirus (MCPyV)-positive and -negative tumors, which show different clinicopathological features and may develop through different mechanisms of carcinogenesis. Aberrant expression of activation-induced cytidine deaminase (AID) as a genomic modulator was demonstrated through pathogen-related NF-κB signal in Helicobacter pylori-associated gastric cancer, adult T cell leukemia/lymphoma (HTLV-1), hepatoma (HCV), and Burkitt lymphoma (EBV)...
September 2017: Yonago Acta Medica
https://www.readbyqxmd.com/read/28939756/efficient-induction-of-ig-gene-hypermutation-in-ex-vivo-activated-primary-b-cells
#18
Jun Liu, Ermeng Xiong, Hanying Zhu, Hiromi Mori, Shoya Yasuda, Kazuo Kinoshita, Takeshi Tsubata, Ji-Yang Wang
Activation-induced cytidine deaminase (AID) initiates both somatic hypermutation (SHM) and class switch recombination (CSR) of Ig genes. How AID is targeted to the Ig V gene and switch region to trigger SHM and CSR remains elusive. Primary B cells stimulated with CD40L plus IL-4 or LPS plus IL-4 undergo efficient CSR, but it has been difficult to induce SHM in these cells. In the current study, we used B cells from B1-8hi mice carrying a prerecombined VH186.2DFL16.1JH2 Ab gene to investigate the induction of SHM under in vitro culture conditions...
November 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28935768/the-microanatomic-segregation-of-selection-by-apoptosis-in-the-germinal-center
#19
Christian T Mayer, Anna Gazumyan, Ervin E Kara, Alexander D Gitlin, Jovana Golijanin, Charlotte Viant, Joy Pai, Thiago Y Oliveira, Qiao Wang, Amelia Escolano, Max Medina-Ramirez, Rogier W Sanders, Michel C Nussenzweig
B cells undergo rapid cell division and affinity maturation in anatomically distinct sites in lymphoid organs called germinal centers (GCs). Homeostasis is maintained in part by B cell apoptosis. However, the precise contribution of apoptosis to GC biology and selection is not well defined. We developed apoptosis-indicator mice and used them to visualize, purify, and characterize dying GC B cells. Apoptosis is prevalent in the GC, with up to half of all GC B cells dying every 6 hours. Moreover, programmed cell death is differentially regulated in the light zone and the dark zone: Light-zone B cells die by default if they are not positively selected, whereas dark-zone cells die when their antigen receptors are damaged by activation-induced cytidine deaminase...
October 13, 2017: Science
https://www.readbyqxmd.com/read/28933967/aid-biology-a-pathological-and-clinical-perspective
#20
Meenal Choudhary, Anubhav Tamrakar, Amit Kumar Singh, Monika Jain, Ankit Jaiswal, Prashant Kodgire
Activation-induced cytidine deaminase (AID), primarily expressed in activated mature B lymphocytes in germinal centers, is the key factor in adaptive immune response against foreign antigens. AID is responsible for producing high-affinity and high-specificity antibodies against an infectious agent, through the physiological DNA alteration processes of antibody genes by somatic hypermutation (SHM) and class-switch recombination (CSR) and functions by deaminating deoxycytidines (dC) to deoxyuridines (dU), thereby introducing point mutations and double-stranded chromosomal breaks (DSBs)...
September 21, 2017: International Reviews of Immunology
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