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Class switch recombination

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https://www.readbyqxmd.com/read/29321331/germline-igm-is-sufficient-but-not-required-for-antibody-mediated-alphavirus-clearance-from-the-central-nervous-system
#1
Voraphoj Nilaratanakul, Jie Chen, Oanh Tran, Victoria K Baxter, Elizabeth M Troisi, Jane X Yeh, Diane E Griffin
Sindbis virus (SINV) infection of neurons in the brain and spinal cord in mice provides a model system for investigating recovery from encephalomyelitis and antibody-mediated clearance of virus from the central nervous system (CNS). To determine the roles of IgM and IgG in recovery, we compared the responses of immunoglobulin-deficient activation-induced adenosine deaminase (AID)-/-, secretory IgM (sIgM)-/- and AID-/- sIgM-/- double knock out (DKO) mice with wild-type (WT) C57BL/6 mice for disease, clearance of infectious virus and viral RNA from brain and spinal cord, antibody responses and B cell infiltration into the CNS...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29311308/dna-double-strand-break-response-factors-influence-end-joining-features-of-igh-class-switch-and-general-translocation-junctions
#2
Rohit A Panchakshari, Xuefei Zhang, Vipul Kumar, Zhou Du, Pei-Chi Wei, Jennifer Kao, Junchao Dong, Frederick W Alt
Ig heavy chain (IgH) class switch recombination (CSR) in B lymphocytes switches IgH constant regions to change antibody functions. CSR is initiated by DNA double-strand breaks (DSBs) within a donor IgH switch (S) region and a downstream acceptor S region. CSR is completed by fusing donor and acceptor S region DSB ends by classical nonhomologous end-joining (C-NHEJ) and, in its absence, by alternative end-joining that is more biased to use longer junctional microhomologies (MHs). Deficiency for DSB response (DSBR) factors, including ataxia telangiectasia-mutated (ATM) and 53BP1, variably impair CSR end-joining, with 53BP1 deficiency having the greatest impact...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29301981/controlling-of-n-alkylpolyamine-analogue-metabolism-by-selective-deuteration
#3
Sebahat Ucal, Merja R Häkkinen, Aino-Liisa Alanne, Leena Alhonen, Jouko Vepsäläinen, Tuomo A Keinänen, Mervi T Hyvönen
Replacing protium with deuterium is an efficient method to modulate drug metabolism. N -alkylated polyamine analogues are polyamine antimetabolites with proven anticancer efficacy. We have characterized earlier the preferred metabolic routes of N1,N12 -diethylspermine (DESpm), N1 -benzyl- N12 -ethylspermine (BnEtSpm) and N1,N12 -dibenzylspermine (DBSpm) by human recombinant spermine oxidase (SMOX) and acetylpolyamine oxidase (APAO). Here we studied the above analogues, their variably deuterated counterparts and their metabolites as substrates and inhibitors of APAO, SMOX, semicarbazide-sensitive amine oxidase (SSAO), diamine oxidase (DAO) and monoamine oxidases...
January 4, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29235109/-double-duty-conventional-dendritic-cells-in-the-amphibian-xenopus-as-the-prototype-for-antigen-presentation-to-b-cells
#4
Harold R Neely, Jacqueline Guo, Emily M Flowers, Michael F Criscitiello, Martin F Flajnik
Two populations of dendritic cells (DCs) are found in mammals, one derived from hematopoietic precursors (conventional/cDC), and another derived from mesenchymal precursors, the follicular DC (FDC); the latter is specialized for antigen presentation to B cells, and has only been definitively demonstrated in mammals. Both cDC and FDC are necessary for induction of germinal centers (GC) and GC-dependent class switch recombination (CSR) and somatic hypermutation (SHM). We demonstrate that in Xenopus, an amphibian in which immunoglobulin CSR and SHM occur without GC formation, a single type of DC has properties of both cDC and FDC, including high expression of MHC class II for the former and display of native antigen at the cell surface for the latter...
December 12, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29200394/-the-igh-3-rr-doctor-jekyll-and-mister-hyde-of-b-cell-maturation-and-lymphomagenesis
#5
Alexis Saintamand, Nour Ghazzaui, Hussein Issaoui, Yves Denizot
The four transcriptional enhancers located in the 3' regulatory region (3'RR) of the IgH locus control the late phases of B-cell maturation, namely IgH locus transcription, somatic hypermutation and class switch recombination. Doctor Jekyll by nature, the 3'RR acts as Mister Hyde in case of oncogenic translocation at the IgH locus taking under its transcriptional control the translocated oncogene. The aim of this review is to show this duality on the basis of the latest scientific advances in the structure and function of the 3'RR and to hIghlight the targeting of the 3'RR as a potential therapeutic approach in mature B-cell lymphomas...
November 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/29191832/molecular-characterization-of-human-anti-hinge-antibodies-derived-from-single-cell-cloning-of-normal-human-b-cells
#6
Tao Huang, Mary Mathieu, Sophia Lee, Xinhua Wang, Yee Seir Kee, Jack J Bevers, Claudio Ciferri, Alberto Estavez, Manda Wong, Nancy Y Chiang, Gerald Nakamura, Randall J Brezski
Anti-hinge antibodies (AHAs) are an autoantibody subclass that, following proteolytic cleavage, recognize cryptic epitopes exposed in the hinge regions of immunoglobulins (Igs) and do not bind to the intact Ig counterpart. AHAs have been postulated to exacerbate chronic inflammatory disorders such as inflammatory bowel disease and rheumatoid arthritis. On the other hand, AHAs may protect against invasive microbial pathogens and cancer. However, despite more than 50 years of study, the origin and specific B cell compartments that express AHAs remain elusive...
November 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29178433/triptolide-inhibits-donor-specific-antibody-production-and-attenuates-mixed-antibody-mediated-renal-allograft-injury
#7
Daqiang Zhao, Siwen Li, Tao Liao, Yuan Wei, Mingyu Liu, Fei Han, Zihuan Luo, Xiaonan Liu, Qiquan Sun
Donor specific antibodies (DSAs) are major mediators of renal allograft injury, and strategies to inhibit DSA are important in promoting long term graft survival. Triptolide exhibits a wide spectrum of anti-inflammatory and immuno- suppressive activities, and in autoimmune diseases it inhibits autoantibody levels. In this study, we investigated the suppressive role of triptolide in the generation of donor specific antibodies in transplant recipients. We found that triptolide treatment of skin allograft recipients in the mouse significantly suppressed the development of circulating anti-donor specific IgG and effectively alleviated DSAs-mediated renal allograft injury, which led to prolonged allograft survival...
November 27, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29177731/topoisomerase-i-and-genome-stability-the-good-and-the-bad
#8
Jang-Eun Cho, Sue Jinks-Robertson
Topoisomerase I (Top1) resolves torsional stress that accumulates during transcription, replication and chromatin remodeling by introducing a transient single-strand break in DNA. The cleavage activity of Top1 has opposing roles, either promoting or destabilizing genome integrity depending on the context. Resolution of transcription-associated negative supercoils, for example, prevents pairing of the nascent RNA with the DNA template (R-loops) as well as DNA secondary structure formation. Reduced Top1 levels thus enhance CAG repeat contraction, somatic hypermutation, and class switch recombination...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29167838/yy1-controls-e%C3%AE-3-rr-dna-loop-formation-and-immunoglobulin-heavy-chain-class-switch-recombination
#9
Parul Mehra, Tatiana Gerasimova, Arindam Basu, Vibha Jha, Anupam Banerjee, Vishal Sindhava, Falon Gray, Corbett T Berry, Ranjan Sen, Michael L Atchison
No abstract text is available yet for this article.
November 29, 2016: Blood Advances
https://www.readbyqxmd.com/read/29164823/immunoglobulin-g-structure-and-functional-implications-of-different-subclass-modifications-in-initiation-and-resolution-of-allergy
#10
REVIEW
Timothy H Scott-Taylor, Stefan-Claudiu Axinia, Sumeya Amin, Ruth Pettengell
IgE and not IgG is usually associated with allergy. IgE lodged on mast cells in skin or gut and basophils in the blood allows for the prolonged duration of allergy through the persistent expression of high affinity IgE receptors. However, many allergic reactions are not dependent on IgE and are generated in the absence of allergen specific and even total IgE. Instead, IgG plasma cells are involved in induction of, and for much of the pathogenesis of, allergic diseases. The pattern of IgG producing plasma cells in atopic children and the tendency for direct or further class switching to IgE are the principle factors responsible for long-lasting sensitization of mast cells in allergic children...
November 21, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29163507/impact-of-chronic-viral-infection-on-t-cell-dependent-humoral-immune-response
#11
REVIEW
Stéphane Rodriguez, Mikaël Roussel, Karin Tarte, Patricia Amé-Thomas
During the last decades, considerable efforts have been done to decipher mechanisms supported by microorganisms or viruses involved in the development, differentiation, and function of immune cells. Pathogens and their associated secretome as well as the continuous inflammation observed in chronic infection are shaping both innate and adaptive immunity. Secondary lymphoid organs are functional structures ensuring the mounting of adaptive immune response against microorganisms and viruses. Inside these organs, germinal centers (GCs) are the specialized sites where mature B-cell differentiation occurs leading to the release of high-affinity immunoglobulin (Ig)-secreting cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29158406/transcriptome-wide-characterization-of-human-cytomegalovirus-in-natural-infection-and-experimental-latency
#12
Shu Cheng, Katie Caviness, Jason Buehler, Megan Smithey, Janko Nikolich-Žugich, Felicia Goodrum
The transcriptional program associated with herpesvirus latency and the viral genes regulating entry into and exit from latency are poorly understood and controversial. Here, we developed and validated a targeted enrichment platform and conducted large-scale transcriptome analyses of human cytomegalovirus (HCMV) infection. We used both an experimental hematopoietic cell model of latency and cells from naturally infected, healthy human subjects (clinical) to define the breadth of viral genes expressed. The viral transcriptome derived from experimental infection was highly correlated with that from clinical infection, validating our experimental latency model...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29158395/histone-methyltransferase-mmset-promotes-aid-mediated-dna-breaks-at-the-donor-switch-region-during-class-switch-recombination
#13
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/29146676/epithelial-immunity-priming-defensive-responses-in-the-intestinal-mucosa
#14
Cristina Pardo-Camacho, Ana Maria González-Castro, Bruno Kotska Rodiño-Janeiro, Marc Pigrau, Maria Vicario
As the largest interface between the outside and internal milieu, the intestinal epithelium constitutes the first structural component facing potential luminal threats to homeostasis. This single-cell layer is the epicenter of a tightly-regulated communication network between external and internal factors which converge to prime defensive responses aimed at limiting antigen penetration and the maintenance of intestinal barrier function. The defensive role developed by intestinal epithelial cells (IEC) relies largely on the variety of receptors they express at both extracellular (apical and basolateral) and intracellular compartments, and the capacity of IEC to communicate with immune and nervous systems...
November 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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