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Class switch recombination

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https://www.readbyqxmd.com/read/27897229/global-gene-regulation-during-activation-of-immunoglobulin-class-switching-in-human-b-cells
#1
Youming Zhang, David J Fear, Saffron A G Willis-Owen, William O Cookson, Miriam F Moffatt
Immunoglobulin class switch recombination (CSR) to IgE is a tightly regulated process central to atopic disease. To profile the B-cell transcriptional responses underlying the activation of the germinal centre activities leading to the generation of IgE, naïve human B-cells were stimulated with IL-4 and anti-CD40. Gene expression and alternative splicing were profiled over 12 days using the Affymetrix Human Exon 1.0 ST Array. A total of 1,399 genes, forming 13 temporal profiles were differentially expressed...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27890643/coordination-of-dna-single-strand-break-repair
#2
Rachel Abbotts, David M Wilson
The genetic material of all organisms is susceptible to modification. In some instances, these changes are programmed, such as the formation of DNA double strand breaks during meiotic recombination to generate gamete variety or class switch recombination to create antibody diversity. However, in most cases, genomic damage is potentially harmful to the health of the organism, contributing to disease and aging by promoting deleterious cellular outcomes. A proportion of DNA modifications are caused by exogenous agents, both physical (namely ultraviolet sunlight and ionizing radiation) and chemical (such as benzopyrene, alkylating agents, platinum compounds and psoralens), which can produce numerous forms of DNA damage, including a range of "simple" and helix-distorting base lesions, abasic sites, crosslinks and various types of phosphodiester strand breaks...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27871841/rubber-particle-proteins-ref1-and-srpp1-interact-differently-with-native-lipids-extracted-from-hevea-brasiliensis-latex
#3
Kanthida Wadeesirisak, Sabine Castano, Karine Berthelot, Laurent Vaysse, Frédéric Bonfils, Frédéric Peruch, Kittipong Rattanaporn, Siriluck Liengprayoon, Sophie Lecomte, Céline Bottier
Rubber particle membranes from the Hevea latex contain predominantly two proteins, REF1 and SRPP1 involved in poly(cis-1,4-isoprene) synthesis or rubber quality. The repartition of both proteins on the small or large rubber particles seems to differ, but their role in the irreversible coagulation of the rubber particle is still unknown. In this study we highlighted the different modes of interactions of both recombinant proteins with different classes of lipids extracted from Hevea brasiliensis latex, and defined as phospholipids (PL), glycolipids (GL) and neutral lipids (NL)...
November 19, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27853268/kin17-facilitates-multiple-double-strand-break-repair-pathways-that-govern-b-cell-class-switching
#4
Michael X Le, Dania Haddad, Alexanda K Ling, Conglei Li, Clare C So, Amit Chopra, Rui Hu, Jaime F Angulo, Jason Moffat, Alberto Martin
Class switch recombination (CSR) in B cells requires the timely repair of DNA double-stranded breaks (DSBs) that result from lesions produced by activation-induced cytidine deaminase (AID). Through a genome-wide RNAi screen, we identified Kin17 as a gene potentially involved in the maintenance of CSR in murine B cells. In this study, we confirm a critical role for Kin17 in CSR independent of AID activity. Furthermore, we make evident that DSBs generated by AID or ionizing radiation require Kin17 for efficient repair and resolution...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27837104/cutting-edge-baff-overexpression-reduces-atherosclerosis-via-taci-dependent-b-cell-activation
#5
Shaun W Jackson, Nicole E Scharping, Holly M Jacobs, Shari Wang, Alan Chait, David J Rawlings
Patients with systemic lupus erythematosus exhibit accelerated atherosclerosis, a chronic inflammatory disease of the arterial wall. The impact of B cells in atherosclerosis is controversial, with both protective and pathogenic roles described. For example, natural IgM binding conserved oxidized lipid epitopes protect against atherosclerosis, whereas anti-oxidized low-density lipoprotein (oxLDL) IgG likely promotes disease. Because BAFF promotes B cell class-switch recombination and humoral autoimmunity, we hypothesized that excess BAFF would accelerate atherosclerosis...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27836054/clinical-phenotypes-of-hyper-igm-syndromes
#6
M Teresa de la Morena
The primary immunodeficiency (PID) diseases comprise a heterogeneous group of inherited disorders of immune function. Technical advancements in whole-genome, whole-exome, and RNA-sequencing have seen the explosion of genetic discoveries in the field of PIDs. The present review aims to focus on a group of immunodeficiency disorders associated with elevated levels of IgM (hyper IgM; HIGM) and provides a clinical differential diagnosis. Most patients present for evaluation of immunodeficiency due to recurrent infections, and laboratory studies show either a clear isolated elevation of serum immunoglobulin M (IgM) with low or absent IgG, IgA, and IgE...
November 2016: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/27835756/regulated-localization-of-an-aid-complex-with-e2a-pax5-and-irf4-at-the-igh-locus
#7
Jannek Hauser, Christine Grundström, Ramesh Kumar, Thomas Grundström
Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates somatic hypermutation (SH) and class switch recombination (CSR) by deaminating cytosine to uracil. The targeting of AID and therefore SH and CSR to Ig genes is a central process of the immune system, but the trans-acting factors mediating the specific targeting have remained elusive. Here we show that defective calmodulin inhibition of the transcription factor E2A after activation of the B cell receptor (BCR) leads to reduced BCR, IL4 plus CD40 ligand stimulated CSR to IgE and instead CSR to other Ig classes...
November 8, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27825459/origin-of-waldenstrom-s-macroglobulinaemia
#8
REVIEW
Ramón García-Sanz, Cristina Jiménez, Noemí Puig, Bruno Paiva, Norma C Gutiérrez, Paula Rodríguez-Otero, Julia Almeida, Jesús San Miguel, Alberto Orfão, Marcos González, Martín Pérez-Andrés
Waldenstrom's macroglobulinaemia (WM) is an MYD88(L265P)-mutated lymphoplasmacytic lymphoma that invades bone marrow and secretes monoclonal immunoglobulin M (IgM). WM cells are usually unable to undergo class switch recombination, and have mutated IGHV, with a typical immunophenotype CD19(+)/CD22(low+)/CD23(-)/CD25(+)/CD27(+)/CD45(+)/CD38(low+)/SmIgM(+) (negative for CD5, CD10, CD11c, CD103). This immunophenotype matches memory B cells (smIgM(-/+)/CD10(-)/CD19(+)/CD20(+)/CD27(+)/CD38(low+)/CD45(+)), representing 30% of B cells in the blood...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27813533/transgenic-mouse-model-of-igm-lymphoproliferative-disease-mimicking-waldenstr%C3%A3-m-macroglobulinemia
#9
V S Tompkins, R Sompallae, T R Rosean, S Walsh, M Acevedo, A L Kovalchuk, S-S Han, X Jing, C Holman, J E Rehg, S Herms, J S Sunderland, H C Morse, S Janz
Waldenström macroglobulinemia (WM) is a low-grade incurable immunoglobulin M(+) (IgM(+)) lymphoplasmacytic lymphoma for which a genetically engineered mouse model of de novo tumor development is lacking. On the basis of evidence that the pro-inflammatory cytokine, interleukin 6 (IL6), and the survival-enhancing oncoprotein, B cell leukemia 2 (BCL2), have critical roles in the natural history of WM, we hypothesized that the enforced expression of IL6 and BCL2 in mice unable to perform immunoglobulin class switch recombination may result in a lymphoproliferative disease that mimics WM...
November 4, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27799928/evaluation-of-the-antigen-experienced-b-cell-receptor-repertoire-in-healthy-children-and-adults
#10
Hanna IJspeert, Pauline A van Schouwenburg, David van Zessen, Ingrid Pico-Knijnenburg, Gertjan J Driessen, Andrew P Stubbs, Mirjam van der Burg
Upon antigen recognition via their B cell receptor (BR), B cells migrate to the germinal center where they undergo somatic hypermutation (SHM) to increase their affinity for the antigen, and class switch recombination (CSR) to change the effector function of the secreted antibodies. These steps are essential to create an antigen-experienced BR repertoire that efficiently protects the body against pathogens. At the same time, the BR repertoire should be selected to protect against responses to self-antigen or harmless antigens...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27798169/germinal-center-hypoxia-potentiates-immunoglobulin-class-switch-recombination
#11
Robert K Abbott, Molly Thayer, Jasmine Labuda, Murillo Silva, Phaethon Philbrook, Derek W Cain, Hidefumi Kojima, Stephen Hatfield, Shalini Sethumadhavan, Akio Ohta, Ellis L Reinherz, Garnett Kelsoe, Michail Sitkovsky
Germinal centers (GCs) are anatomic sites where B cells undergo secondary diversification to produce high-affinity, class-switched Abs. We hypothesized that proliferating B cells in GCs create a hypoxic microenvironment that governs their further differentiation. Using molecular markers, we found GCs to be predominantly hypoxic. Compared to normoxia (21% O2), hypoxic culture conditions (1% O2) in vitro accelerated class switching and plasma cell formation and enhanced expression of GL-7 on B and CD4(+) T cells...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27777312/mbd4-facilitates-immunoglobulin-class-switch-recombination
#12
Fernando Grigera, Robert Wuerffel, Amy L Kenter
Immunoglobulin heavy chain class switch recombination (CSR) requires targeted formation of DNA double strand breaks (DSBs) in repetitive switch region elements followed by ligation between distal breaks. The introduction of DSBs is initiated by activation induced cytidine deaminase (AID) and requires base excision repair (BER) and mismatch repair (MMR). The BER enzyme, methyl CpG binding domain protein 4 (MBD4) has been linked to the MMR pathway through its interaction with MutL homologue 1 (MLH1). We find that when the Mbd4 exons 6-8 are deleted in a switching B cell line DSB formation is severely reduced and CSR frequency is impaired...
October 24, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27761815/effects-of-hdaci-on-immunological-functions
#13
René Winkler, Christian Kosan
Histone deacetylase inhibitors (HDACi) are used as therapeutics for several B cell-derived malignancies. Furthermore, they have been shown to modulate the response of the immune system, like the B cell function. HDACi treatment affects differentiation, proliferation, and survival of B cells. Here we describe how to investigate the effects of HDACi treatment on naïve B cells regarding class-switch recombination (CSR) in vitro using flow cytometry.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27721128/a-single-intranasal-immunization-with-a-subunit-vaccine-formulation-induces-higher-mucosal-iga-production-than-live-respiratory-syncytial-virus
#14
Ravendra Garg, Michael Theaker, Elisa C Martinez, Sylvia van Drunen Littel-van den Hurk
Respiratory syncytial virus (RSV) causes serious respiratory illness in infants and elderly. RSV infection induces short-lived immunity, which leaves people prone to re-infection. In contrast, the RSV fusion (F) protein formulated with a novel adjuvant (∆F/TriAdj) elicits long term protective immunity. A comparison of RSV-immunized mice to mice vaccinated with a single dose of ∆F/TriAdj showed no difference in IgG1 and IgG2a production; however, local IgA secreting memory B cell development and B cell IgA production were significantly lower in RSV vaccinated mice than in ∆F/TriAdj-immunized mice...
October 6, 2016: Virology
https://www.readbyqxmd.com/read/27721014/genetically-encoding-new-bioreactivity
#15
Lei Wang
The genetic code can be expanded to include unnatural amino acids (Uaas) by engineering orthogonal components involved in protein translation. To be compatible with live cells, side chains of Uaas have been limited to either chemically inert or bio-orthogonal (i.e., nonreactive toward biomolecules) functionalities. To introduce bioreactivity into live systems, the genetic code has recently been engineered to encode a new class of Uaas, the bioreactive Uaas. These Uaas, after being incorporated into proteins, specifically react with target natural amino acid residues via proximity-enabled bioreactivity, enabling the selective formation of new covalent linkages within and between proteins both in vitro and in live systems...
October 6, 2016: New Biotechnology
https://www.readbyqxmd.com/read/27716525/activation-induced-cytidine-deaminase-mutant-aid-his130pro-from-hyper-igm-2-patient-retained-mutagenic-activity-on-shm-artificial-substrate
#16
Hanen Ouadani, Imen Ben-Mustapha, Meriem Ben-Ali, Beya Larguèche, Tihana Jovanic, Sylvie Garcia, Benoit Arcangioli, Houda Elloumi-Zghal, Dahmani Fathallah, Mongia Hachicha, Hatem Masmoudi, François Rougeon, Mohamed-Ridha Barbouche
Activation induced cytidine deaminase (AID) is an essential enzyme for class switch recombination (CSR) and somatic hypermutation (SHM) during secondary immune response. Mutations in the AICDA gene are responsible for Hyper IgM 2 syndrome where both CSR and SHM or only CSR are affected. Indeed, triggering either of the two mechanisms requires the DNA deamination activity of AID. Besides, different domains of AID may be differentially involved in CSR and SHM through their interaction with specific cofactors...
October 4, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27713077/noninfectious-complications-in-patients-with-pediatric-onset-common-variable-immunodeficiency-correlated-with-defects-in-somatic-hypermutation-but-not-in-class-switch-recombination
#17
María Belén Almejún, Bárbara Carolina Campos, Virginia Patiño, Miguel Galicchio, Marta Zelazko, Matías Oleastro, Pablo Oppezzo, Silvia Danielian
BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impaired immunoglobulin production and usually presents with a normal quantity of peripheral B cells. Most attempts aiming to classify these patients have mainly been focused on T- or B-cell phenotypes and their ability to produce protective antibodies, but it is still a major challenge to find a suitable classification that includes the clinical and immunologic heterogeneity of these patients...
October 3, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27701145/decreased-somatic-hypermutation-induces-an-impaired-peripheral-b-cell-tolerance-checkpoint
#18
Tineke Cantaert, Jean-Nicolas Schickel, Jason M Bannock, Yen-Shing Ng, Christopher Massad, Fabien R Delmotte, Natsuko Yamakawa, Salome Glauzy, Nicolas Chamberlain, Tuure Kinnunen, Laurence Menard, Aubert Lavoie, Jolan E Walter, Luigi D Notarangelo, Julie Bruneau, Waleed Al-Herz, Sara Sebnem Kilic, Hans D Ochs, Charlotte Cunningham-Rundles, Mirjam van der Burg, Taco W Kuijpers, Sven Kracker, Hideo Kaneko, Yujin Sekinaka, Shigeaki Nonoyama, Anne Durandy, Eric Meffre
Patients with mutations in AICDA, which encodes activation-induced cytidine deaminase (AID), display an impaired peripheral B cell tolerance. AID mediates class-switch recombination (CSR) and somatic hypermutation (SHM) in B cells, but the mechanism by which AID prevents the accumulation of autoreactive B cells in blood is unclear. Here, we analyzed B cell tolerance in AID-deficient patients, patients with autosomal dominant AID mutations (AD-AID), asymptomatic AICDA heterozygotes (AID+/-), and patients with uracil N-glycosylase (UNG) deficiency, which impairs CSR but not SHM...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27701075/a-double-strand-break-can-trigger-immunoglobulin-gene-conversion
#19
Giulia Bastianello, Hiroshi Arakawa
All three B cell-specific activities of the immunoglobulin (Ig) gene re-modeling system-gene conversion, somatic hypermutation and class switch recombination-require activation-induced deaminase (AID). AID-induced DNA lesions must be further processed and dissected into different DNA recombination pathways. In order to characterize potential intermediates for Ig gene conversion, we inserted an I-SceI recognition site into the complementarity determining region 1 (CDR1) of the Ig light chain locus of the AID knockout DT40 cell line, and conditionally expressed I-SceI endonuclease...
October 3, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27649663/the-involvement-of-igh-enhancer-hs1-2-in-the-pathogenesis-of-crohn-s-disease-how-the-immune-system-can-influence-a-multifactorial-disease
#20
R Cianci, S Lolli, D Pagliari, G Gambassi, S Frosali, R Marmo, G Melioli, A Orlando, E E Newton, E Serone, R Landolfi, F Pandolfi, D Frezza
OBJECTIVE: To study the 3' immunoglobulin heavy-chain regulatory region (3'RR) enhancer complex, active in class switching recombination and in B-cells, in Crohn's disease. PATIENTS AND METHODS: A total of 167 patients [79 females (47.3%) and 88 males (52.7%)] affected by Crohn's disease were enrolled in the study. As a control, we included 64 healthy subjects, age and sex matched, from the same geographical area. Blood tests were performed on all subjects to determine their antibody levels and to detect the presence of any possible infections...
September 2016: European Review for Medical and Pharmacological Sciences
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