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Class switch recombination

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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
#1
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
#2
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...
November 9, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29109124/endogenous-calcitriol-synthesis-controls-the-humoral-ige-response-in-mice
#3
Juliane Lindner, Sebastian Rausch, Sandra Treptow, Kerstin Geldmeyer-Hilt, Tina Krause, René St-Arnaud, Alice Arabian, Andreas Radbruch, Susanne Hartmann, Margitta Worm, Guido Heine
The vitamin D receptor participates in the control of IgE class-switch recombination in B cells. The physiologic vitamin D receptor agonist, 1,25(OH)2D3 (calcitriol), is synthesized by the essential enzyme 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1), which can be expressed by activated immune cells. The role of endogenous calcitriol synthesis for the regulation of IgE has not been proven. In this study, we investigated IgE-responses in Cyp27b1-knockout (KO) mice following sensitization to OVA or intestinal infection with Heligmosomoides polygyrus Specific Igs and plasmablasts were determined by ELISA and ELISpot, Cyp27b1 expression was measured by quantitative PCR...
November 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29101850/microrna-146a-promotes-ige-class-switch-in-b-cells-via-upregulating-14-3-3%C3%AF-expression
#4
Fei Li, Yi Huang, You-Ying Huang, Yan-Song Kuang, Yong-Jian Wei, Li Xiang, Xing-Ju Zhang, Zheng-Cai Jia, Shan Jiang, Jing-Yi Li, Ying Wan
B cells play a critical role in immune responses both in physiological and pathological conditions, and microRNAs have been shown to play important roles in regulating B cell proliferation and function. MiR-146a has been shown to modulate T cell immunity, but its function in regulating B cell response remains partially understood. Our previous studies indicated that germinal center (GC) B cells are significantly expanded in miR-146a-overexpressing (TG) mice. In this study, we further characterized the roles of miR-146a in regulating humoral immune responses to specific antigens...
November 1, 2017: Molecular Immunology
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
#5
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/29098565/immunodeficiency-in-bloom-s-syndrome
#6
Michiel H D Schoenaker, Stefanie S Henriet, Jip Zonderland, Marcel van Deuren, Qiang Pan-Hammarström, Sandra J Posthumus-van Sluijs, Ingrid Pico-Knijnenburg, Corry M R Weemaes, Hanna IJspeert
Bloom's syndrome (BS) is an autosomal recessive disease, caused by mutations in the BLM gene. This gene codes for BLM protein, which is a helicase involved in DNA repair. DNA repair is especially important for the development and maturation of the T and B cells. Since BLM is involved in DNA repair, we aimed to study if BLM deficiency affects T and B cell development and especially somatic hypermutation (SHM) and class switch recombination (CSR) processes. Clinical data of six BS patients was collected, and immunoglobulin serum levels were measured at different time points...
November 2, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29080214/transcription-factor-yy1-can-control-aid-mediated-mutagenesis-in-mice
#7
Kristina Zaprazna, Arindam Basu, Nikola Tom, Vibha Jha, Suchita Hodawadekar, Lenka Radova, Jitka Malcikova, Boris Tichy, Sarka Pospisilova, Michael L Atchison
Activation-induced cytidine deminase (AID) is crucial for controlling the immunoglobulin (Ig) diversification processes of somatic hypermutation (SHM) and class switch recombination (CSR). AID initiates these processes by deamination of cytosine, ultimately resulting in mutations or double strand DNA breaks needed for SHM and CSR. Levels of AID control mutation rates, and off-target non-Ig gene mutations can contribute to lymphomagenesis. Therefore, factors that control AID levels in the nucleus can regulate SHM and CSR, and may contribute to disease...
October 28, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29042055/mechanism-underlying-the-suppressor-activity-of-retinoic-acid-on-il4-induced-ige-synthesis-and-its-physiological-implication
#8
Goo-Young Seo, Jeong-Min Lee, Young-Saeng Jang, Seung Goo Kang, Sung-Il Yoon, Hyun-Jeong Ko, Geun-Shik Lee, Seok-Rae Park, Cathryn R Nagler, Pyeung-Hyeun Kim
The present study extends an earlier report that retinoic acid (RA) down-regulates IgE Ab synthesis in vitro. Here, we show the suppressive activity of RA on IgE production in vivo and its underlying mechanisms. We found that RA down-regulated IgE class switching recombination (CSR) mainly through RA receptor α (RARα). Additionally, RA inhibited histone acetylation of germ-line ε (GL ε) promoter, leading to suppression of IgE CSR. Consistently, serum IgE levels were substantially elevated in vitamin A-deficient (VAD) mice and this was more dramatic in VAD-lecithin:retinol acyltransferase deficient (LRAT(-/-)) mice...
October 3, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29031828/non-progressing-cancer-patients-have-persistent-b-cell-responses-expressing-shared-antibody-paratopes-that-target-public-tumor-antigens
#9
Jeff DeFalco, Michael Harbell, Amy Manning-Bog, Gilson Baia, Alexander Scholz, Beatriz Millare, May Sumi, Danhui Zhang, Felix Chu, Christine Dowd, Patricia Zuno-Mitchell, Dongkyoon Kim, Yvonne Leung, Shuwei Jiang, Xiaobin Tang, Kevin S Williamson, Xiaomu Chen, Sean M Carroll, Gregg Espiritu Santo, Nicole Haaser, Ngan Nguyen, Eldar Giladi, David Minor, Yann Chong Tan, Jeremy B Sokolove, Lawrence Steinman, Tito A Serafini, Guy Cavet, Norman M Greenberg, Jacob Glanville, Wayne Volkmuth, Daniel E Emerling, William H Robinson
There is significant debate regarding whether B cells and their antibodies contribute to effective anti-cancer immune responses. Here we show that patients with metastatic but non-progressing melanoma, lung adenocarcinoma, or renal cell carcinoma exhibited increased levels of blood plasmablasts. We used a cell-barcoding technology to sequence their plasmablast antibody repertoires, revealing clonal families of affinity matured B cells that exhibit progressive class switching and persistence over time. Anti-CTLA4 and other treatments were associated with further increases in somatic hypermutation and clonal family size...
October 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29026218/igd-class-switch-recombination-is-not-controlled-through-the-immunoglobulin-heavy-chain-3-regulatory-region-super-enhancer
#10
Hussein Issaoui, Nour Ghazzaui, Alexis Saintamand, Yves Denizot, François Boyer
No abstract text is available yet for this article.
October 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28994753/genome-wide-analysis-of-hdac-inhibitor-mediated-modulation-of-micrornas-and-mrnas-in-b-cells-induced-to-undergo-class-switch-dna-recombination-and-plasma-cell-differentiation
#11
Helia N Sanchez, Tian Shen, Dawn Garcia, Zhao Lai, Paolo Casali, Hong Zan
Antibody responses are accomplished through several critical B cell-intrinsic processes, including somatic hypermutation (SHM), class-switch DNA recombination (CSR), and plasma cell differentiation. In recent years, epigenetic modifications or factors, such as histone deacetylation and microRNAs (miRNAs), have been shown to interact with B-cell genetic programs to shape antibody responses, while the dysfunction of epigenetic factors has been found to lead to autoantibody responses. Analyzing genome-wide miRNA and mRNA expression in B cells in response to epigenetic modulators is important for understanding the epigenetic regulation of B-cell function and antibody response...
September 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28993481/mtor-bach2-cascade-controls-cell-cycle-and-class-switch-recombination-during-b-cell-differentiation
#12
Toru Tamahara, Kyoko Ochiai, Akihiko Muto, Yukinari Kato, Nicolas Sax, Mitsuyo Matsumoto, Takeyoshi Koseki, Kazuhiko Igarashi
The transcription factor Bach2 regulates both acquired and innate immunity at multiple steps including antibody class switching and regulatory T cell development in activated B and T cells, respectively. However, little is known about the molecular mechanisms of Bach2 regulation in response to signaling of cytokines and antigen. We show here that mammalian target of rapamycin (mTOR) controls Bach2 along B cell differentiation with two distinct mechanisms in pre-B cells. Firstly, mTOR complex 1 (mTORC1) inhibited accumulation of Bach2 protein in nuclei and reduced its stability...
October 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28990584/the-igh-3-regulatory-region-super-enhancer-does-not-control-iga-class-switch-recombination-in-the-b1-lineage
#13
Hussein Issaoui, Nour Ghazzaui, Alexis Saintamand, Claire Carrion, Christelle Oblet, Yves Denizot
No abstract text is available yet for this article.
October 9, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28955333/accelerated-systemic-autoimmunity-in-the-absence-of-somatic-hypermutation-in-564igi-a-mouse-model-of-systemic-lupus-with-knocked-in-heavy-and-light-chain-genes
#14
Gabrielle McDonald, Carlos O Medina, Monika Pilichowska, John F Kearney, Reiko Shinkura, Erik Selsing, Henry H Wortis, Tasuku Honjo, Thereza Imanishi-Kari
564Igi mice have knocked-in immunoglobulin (Ig) heavy (H) and light (L) chain genes that encode an autoantibody recognizing RNA. Previously, we showed that these mice produce pathogenic IgG autoantibodies when activation-induced deaminase (AID) is expressed in pre-B and immature B cells but not when it is expressed only in mature B cells. AID has two functions; it is necessary for somatic hypermutation (SHM) and class switch recombination (CSR). To determine the role of each of these functions in the generation of pathogenic autoantibodies, we generated 564Igi mice that carry a mutant AID-encoding gene, Aicda (Aicda(G23S)), which is capable of promoting CSR but not SHM...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28953967/malaria-induced-interferon-%C3%AE-drives-the-expansion-of-tbethi-atypical-memory-b-cells
#15
Nyamekye Obeng-Adjei, Silvia Portugal, Prasida Holla, Shanping Li, Haewon Sohn, Abhijit Ambegaonkar, Jeff Skinner, Georgina Bowyer, Ogobara K Doumbo, Boubacar Traore, Susan K Pierce, Peter D Crompton
Many chronic infections, including malaria and HIV, are associated with a large expansion of CD21-CD27- 'atypical' memory B cells (MBCs) that exhibit reduced B cell receptor (BCR) signaling and effector functions. Little is known about the conditions or transcriptional regulators driving atypical MBC differentiation. Here we show that atypical MBCs in malaria-exposed individuals highly express the transcription factor T-bet, and that T-bet expression correlates inversely with BCR signaling and skews toward IgG3 class switching...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28939756/efficient-induction-of-ig-gene-hypermutation-in-ex-vivo-activated-primary-b-cells
#16
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 B1-8(hi) 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/28935935/igg1-memory-b-cells-keep-the-memory-of-ige-responses
#17
Jin-Shu He, Sharrada Subramaniam, Vipin Narang, Kandhadayar Srinivasan, Sean P Saunders, Daniel Carbajo, Tsao Wen-Shan, Nur Hidayah Hamadee, Josephine Lum, Andrea Lee, Jinmiao Chen, Michael Poidinger, Francesca Zolezzi, Juan J Lafaille, Maria A Curotto de Lafaille
The unique differentiation of IgE cells suggests unconventional mechanisms of IgE memory. IgE germinal centre cells are transient, most IgE cells are plasma cells, and high affinity IgE is produced by the switching of IgG1 cells to IgE. Here we investigate the function of subsets of IgG1 memory B cells in IgE production and find that two subsets of IgG1 memory B cells, CD80(+)CD73(+) and CD80(-)CD73(-), contribute distinctively to the repertoires of high affinity pathogenic IgE and low affinity non-pathogenic IgE...
September 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28933967/aid-biology-a-pathological-and-clinical-perspective
#18
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
https://www.readbyqxmd.com/read/28928744/ccctc-binding-factor-locks-premature-igh-germline-transcription-and-restrains-class-switch-recombination
#19
Ester Marina-Zárate, Arantxa Pérez-García, Almudena R Ramiro
In response to antigenic stimulation B cells undergo class switch recombination (CSR) at the immunoglobulin heavy chain (IgH) to replace the primary IgM/IgD isotypes by IgG, IgE, or IgA. CSR is initiated by activation-induced cytidine deaminase (AID) through the deamination of cytosine residues at the switch (S) regions of IgH. B cell stimulation promotes germline transcription (GLT) of specific S regions, a necessary event prior to CSR because it facilitates AID access to S regions. Here, we show that CCCTC-binding factor (CTCF)-deficient mice are severely impaired in the generation of germinal center B cells and plasma cells after immunization in vivo, most likely due to impaired cell survival...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28867784/the-complex-interplay-between-dna-injury-and-repair-in-enzymatically-induced-mutagenesis-and-dna-damage-in-b-lymphocytes
#20
REVIEW
Mahnoush Bahjat, Jeroen E J Guikema
Lymphocytes are endowed with unique and specialized enzymatic mutagenic properties that allow them to diversify their antigen receptors, which are crucial sensors for pathogens and mediators of adaptive immunity. During lymphocyte development, the antigen receptors expressed by B and T lymphocytes are assembled in an antigen-independent fashion by ordered variable gene segment recombinations (V(D)J recombination), which is a highly ordered and regulated process that requires the recombination activating gene products 1 & 2 (RAG1, RAG2)...
August 30, 2017: International Journal of Molecular Sciences
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