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Class switch recombination

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https://www.readbyqxmd.com/read/29744038/generating-and-repairing-genetically-programmed-dna-breaks-during-immunoglobulin-class-switch-recombination
#1
REVIEW
Laura Nicolas, Montserrat Cols, Jee Eun Choi, Jayanta Chaudhuri, Bao Vuong
Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR...
2018: F1000Research
https://www.readbyqxmd.com/read/29739685/b-cell-subsets-imbalance-and-reduced-expression-of-cd40-in-ataxia-telangiectasia-patients
#2
C T M Pereira, D C Bichuetti-Silva, N V F da Mota, R Salomão, M K C Brunialti, B T Costa-Carvalho
BACKGROUND: Ataxia-telangiectasia (AT) is a well-known primary immunodeficiency with recurrent sinopulmonary infections and variable abnormalities in both the humoral and cellular immune system. Dysfunctions in immunoglobulin production, reduced number of B cells, and B-cell receptor excision circles copies have been reported. We aimed to understand the immunological mechanisms involving the humoral compartment in AT patients by analysing peripheral blood B cells subsets, B-T lymphocyte cooperation through the expression of CD40 and CD40 ligand (CD40L), and cytokines involved in class-switch recombination production...
May 5, 2018: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/29735979/uracil-dna-glycosylase-is-not-implicated-in-the-choice-of-the-dna-repair-pathway-during-b-cell-class-switch-recombination
#3
Nour Ghazzaui, Hussein Issaoui, Alexis Saintamand, Yves Denizot, François Boyer
No abstract text is available yet for this article.
May 7, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29731414/rna-helicase-ddx1-converts-rna-g-quadruplex-structures-into-r-loops-to-promote-igh-class-switch-recombination
#4
Claudia Ribeiro de Almeida, Somdutta Dhir, Ashish Dhir, Amin E Moghaddam, Quentin Sattentau, Anton Meinhart, Nicholas J Proudfoot
Class switch recombination (CSR) at the immunoglobulin heavy-chain (IgH) locus is associated with the formation of R-loop structures over switch (S) regions. While these often occur co-transcriptionally between nascent RNA and template DNA, we now show that they also form as part of a post-transcriptional mechanism targeting AID to IgH S-regions. This depends on the RNA helicase DDX1 that is also required for CSR in vivo. DDX1 binds to G-quadruplex (G4) structures present in intronic switch transcripts and converts them into S-region R-loops...
April 30, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29728513/regulation-of-the-dna-repair-complex-during-somatic-hypermutation-and-class-switch-recombination
#5
Anjani Kumar, Anshu Priya, Tanzeel Ahmed, Christine Grundström, Neema Negi, Thomas Grundström
B lymphocytes optimize Ab responses by somatic hypermutation (SH), which introduces point mutations in the variable regions of the Ab genes and by class-switch recombination (CSR), which changes the expressed C region exon of the IgH. These Ab diversification processes are initiated by the deaminating enzyme activation-induced cytidine deaminase followed by many DNA repair enzymes, ultimately leading to deletions and a high mutation rate in the Ab genes, whereas DNA lesions made by activation-induced cytidine deaminase are repaired with low error rate on most other genes...
May 4, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29728506/abrogation-of-lupus-nephritis-in-somatic-hypermutation-deficient-mrl-lpr-mice
#6
Fengqi Hao, Miaomiao Tian, Yunpeng Feng, Chao Quan, Yixi Chen, Shuai Chen, Min Wei
Systemic lupus erythematosus (SLE) is an autoimmune disease posing threats to multiple organs in the human body. As a typical manifestation of SLE, lupus nephritis is characterized by a series of pathological changes in glomerulus as well as accumulation of pathogenic autoreactive IgG with complement in the kidney that dramatically disrupts renal functions. Activation-induced deaminase (AID), which governs both somatic hypermutation (SHM) and class-switch recombination (CSR), has been shown to be essential for the regulation of SLE...
May 4, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29716522/the-cytidine-deaminase-under-representation-reporter-cdur-as-a-tool-to-study-evolution-of-sequences-under-deaminase-mutational-pressure
#7
Maxwell Shapiro, Stephen Meier, Thomas MacCarthy
BACKGROUND: Activation induced deaminase (AID) and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) are deaminases that mutate C to U on single-stranded DNA (ssDNA). AID is expressed primarily in germinal center B-cells, where it facilitates affinity maturation and class-switch recombination. APOBEC3 are a family of anti-viral proteins that act as part of the intrinsic immune response. In both cases, there are particular sequence motifs, also known as "mutation motifs", to which these deaminases prefer to bind and mutate...
May 2, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29704159/diversity-of-immunoglobulin-ig-isotypes-and-the-role-of-activation-induced-cytidine-deaminase-aid-in-fish
#8
REVIEW
Bhakti Patel, Rajanya Banerjee, Mrinal Samanta, Surajit Das
The disparate diversity in immunoglobulin (Ig) repertoire has been a subject of fascination since the emergence of prototypic adaptive immune system in vertebrates. The carboxy terminus region of activation-induced cytidine deaminase (AID) has been well established in tetrapod lineage and is crucial for its function in class switch recombination (CSR) event of Ig diversification. The absence of CSR in the paraphyletic group of fish is probably due to changes in catalytic domain of AID and lack of cis-elements in IgH locus...
April 27, 2018: Molecular Biotechnology
https://www.readbyqxmd.com/read/29691398/galectin-3-deficiency-drives-lupus-like-disease-by-promoting-spontaneous-germinal-centers-formation-via-ifn-%C3%AE
#9
Cristian Gabriel Beccaria, María Carolina Amezcua Vesely, Facundo Fiocca Vernengo, Ricardo Carlos Gehrau, María Cecilia Ramello, Jimena Tosello Boari, Melisa Gorosito Serrán, Juan Mucci, Eliane Piaggio, Oscar Campetella, Eva Virginia Acosta Rodríguez, Carolina Lucía Montes, Adriana Gruppi
Germinal centers (GC) are important sites for high-affinity and long-lived antibody induction. Tight regulation of GC responses is critical for maintaining self-tolerance. Here, we show that Galectin-3 (Gal-3) is involved in GC development. Compared with WT mice, Gal-3 KO mice have more GC B cells and T follicular helper cells, increased percentages of antibody-secreting cells and higher concentrations of immunoglobulins and IFN-γ in serum, and develop a lupus-like disease. IFN-γ blockade in Gal-3 KO mice reduces spontaneous GC formation, class-switch recombination, autoantibody production and renal pathology, demonstrating that IFN-γ overproduction sustains autoimmunity...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29691337/identification-of-the-i38t-pa-substitution-as-a-resistance-marker-for-next-generation-influenza-virus-endonuclease-inhibitors
#10
Jeremy C Jones, Gyanendra Kumar, Subrata Barman, Isabel Najera, Stephen W White, Richard J Webby, Elena A Govorkova
The clinical severity and annual occurrence of influenza virus epidemics, combined with the availability of just a single class of antivirals to treat infections, underscores the urgent need to develop new anti-influenza drugs. The endonuclease activity within the viral acidic polymerase (PA) protein is an attractive target for drug discovery due to the critical role it plays in viral gene transcription. RO-7 is a next-generation PA endonuclease inhibitor of influenza A and B viruses, but its drug resistance potential is unknown...
April 24, 2018: MBio
https://www.readbyqxmd.com/read/29686053/identification-of-a-transcriptionally-forward-%C3%AE-gene-and-two-%C3%AF-genes-within-the-pigeon-columba-livia-igh-gene-locus
#11
Tian Huang, Xifeng Wang, Run Si, Hao Chi, Binyue Han, Haitang Han, Gengsheng Cao, Yaofeng Zhao
Compared with mammals, the bird Ig genetic system relies on gene conversion to create an Ab repertoire, with inversion of the IgA-encoding gene and very few cases of Ig subclass diversification. Although gene conversion has been studied intensively, class-switch recombination, a mechanism by which the IgH C region is exchanged, has rarely been investigated in birds. In this study, based on the published genome of pigeon ( Columba livia ) and high-throughput transcriptome sequencing of immune-related tissues, we identified a transcriptionally forward α gene and found that the pigeon IgH gene locus is arranged as μ-α-υ1-υ2...
April 23, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29665088/gain-of-function-analysis-of-cis-acting-diversification-elements-in-dt40-cells
#12
Randolph B Caldwell, Herbert Braselmann, Steffen Heuer, Ulrike Schötz, Horst Zitzelsberger
Activation-induced cytidine deaminase (AID) is required for the immunoglobulin diversification processes of somatic hypermutation, gene conversion and class-switch recombination. The targeting of AID's deamination activity is thought to be a combination of cis- and trans-acting elements, but has not been fully elucidated. Deletion analysis of putative proximal cis-regulatory motifs, while helpful, fails to identify additive versus cumulative effects, redundancy, and may create new motifs where none previously existed...
April 17, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29658467/-the-enigmatic-igd-class-switch-recombination
#13
Hussein Issaoui, Nour Ghazzaui, Yves Denizot
No abstract text is available yet for this article.
April 2018: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/29656893/dna-repair-network-analysis-reveals-shieldin-as-a-key-regulator-of-nhej-and-parp-inhibitor-sensitivity
#14
Rajat Gupta, Kumar Somyajit, Takeo Narita, Elina Maskey, Andre Stanlie, Magdalena Kremer, Dimitris Typas, Michael Lammers, Niels Mailand, Andre Nussenzweig, Jiri Lukas, Chunaram Choudhary
Repair of damaged DNA is essential for maintaining genome integrity and for preventing genome-instability-associated diseases, such as cancer. By combining proximity labeling with quantitative mass spectrometry, we generated high-resolution interaction neighborhood maps of the endogenously expressed DNA repair factors 53BP1, BRCA1, and MDC1. Our spatially resolved interaction maps reveal rich network intricacies, identify shared and bait-specific interaction modules, and implicate previously concealed regulators in this process...
May 3, 2018: Cell
https://www.readbyqxmd.com/read/29593723/analyzing-immunoglobulin-repertoires
#15
REVIEW
Neha Chaudhary, Duane R Wesemann
Somatic assembly of T cell receptor and B cell receptor (BCR) genes produces a vast diversity of lymphocyte antigen recognition capacity. The advent of efficient high-throughput sequencing of lymphocyte antigen receptor genes has recently generated unprecedented opportunities for exploration of adaptive immune responses. With these opportunities have come significant challenges in understanding the analysis techniques that most accurately reflect underlying biological phenomena. In this regard, sample preparation and sequence analysis techniques, which have largely been borrowed and adapted from other fields, continue to evolve...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29593215/a-licensing-step-links-aid-to-transcription-elongation-for-mutagenesis-in-b-cells
#16
Stephen P Methot, Ludivine C Litzler, Poorani Ganesh Subramani, Anil K Eranki, Heather Fifield, Anne-Marie Patenaude, Julian C Gilmore, Gabriel E Santiago, Halil Bagci, Jean-François Côté, Mani Larijani, Ramiro E Verdun, Javier M Di Noia
Activation-induced deaminase (AID) mutates the immunoglobulin (Ig) genes to initiate somatic hypermutation (SHM) and class switch recombination (CSR) in B cells, thus underpinning antibody responses. AID mutates a few hundred other loci, but most AID-occupied genes are spared. The mechanisms underlying productive deamination versus non-productive AID targeting are unclear. Here we show that three clustered arginine residues define a functional AID domain required for SHM, CSR, and off-target activity in B cells without affecting AID deaminase activity or Escherichia coli mutagenesis...
March 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29572544/high-throughput-sequencing-reveals-similar-molecular-signatures-for-class-switch-recombination-junctions-for-the-%C3%AE-and-%C3%AE-isotypes
#17
Hussein Issaoui, Nour Ghazzaui, Alexis Saintamand, Yves Denizot, François Boyer
No abstract text is available yet for this article.
March 23, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29555777/expansions-diversification-and-interindividual-copy-number-variations-of-aid-apobec-family-cytidine-deaminase-genes-in-lampreys
#18
Stephen J Holland, Lesley M Berghuis, Justin J King, Lakshminarayan M Iyer, Katarzyna Sikora, Heather Fifield, Sarah Peter, Emma M Quinlan, Fumiaki Sugahara, Prashant Shingate, Inês Trancoso, Norimasa Iwanami, Elena Temereva, Christine Strohmeier, Shigeru Kuratani, Byrappa Venkatesh, Guillaume Evanno, L Aravind, Michael Schorpp, Mani Larijani, Thomas Boehm
Cytidine deaminases of the AID/APOBEC family catalyze C-to-U nucleotide transitions in mRNA or DNA. Members of the APOBEC3 branch are involved in antiviral defense, whereas AID contributes to diversification of antibody repertoires in jawed vertebrates via somatic hypermutation, gene conversion, and class switch recombination. In the extant jawless vertebrate, the lamprey, two members of the AID/APOBEC family are implicated in the generation of somatic diversity of the variable lymphocyte receptors (VLRs). Expression studies linked CDA1 and CDA2 genes to the assembly of VLRA /C genes in T-like cells and the VLRB genes in B-like cells, respectively...
April 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29541074/pten-regulated-aid-transcription-in-germinal-center-b-cells-is-essential-for-the-class-switch-recombination-and-igg-antibody-responses
#19
Jing Wang, Sichen Liu, Baidong Hou, Meixiang Yang, Zhongjun Dong, Hai Qi, Wanli Liu
Class-switch recombination (CSR) and somatic hypermutation (SHM) occur during the differentiation of germinal center B cells (GCBs). Activation-induced cytidine deaminase (AID) is responsible for both CSR and SHM in GCBs. Here, we show that ablation of PTEN through the Cγ1-Cre mediated recombination significantly influences the CSR and SHM responses. The GCs fail to produce the IgG1 B cells, the high affinity antibodies and nearly lost the dark zone (DZ) in Ptenfl/fl Cγ1Cre/+ mice after immunization, suggesting the impaired GC structure...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29540581/bach2-promotes-b-cell-receptor-induced-proliferation-of-b-lymphocytes-and-represses-cyclin-dependent-kinase-inhibitors
#20
Yuichi Miura, Mizuho Morooka, Nicolas Sax, Rahul Roychoudhuri, Ari Itoh-Nakadai, Andrey Brydun, Ryo Funayama, Keiko Nakayama, Susumu Satomi, Mitsuyo Matsumoto, Kazuhiko Igarashi, Akihiko Muto
BTB and CNC homology 2 (Bach2) is a transcriptional repressor that is required for the formation of the germinal center (GC) and reactions, including class switch recombination and somatic hypermutation of Ig genes in B cells, within the GC. Although BCR-induced proliferation is essential for GC reactions, the function of Bach2 in regulating B cell proliferation has not been elucidated. In this study, we demonstrate that Bach2 is required to sustain high levels of B cell proliferation in response to BCR signaling...
April 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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