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Isotype switching

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https://www.readbyqxmd.com/read/29132233/prospects-for-modulating-the-cd40-cd40l-pathway-in-the-therapy-of-the-hyper-igm-syndrome
#1
Xiangxue Meng, Bin Yang, Wen-Chen Suen
The critical role of the CD40/CD40L pathway in B-cell proliferation, immunoglobulin (Ig) isotype switching and germinal center formation has been studied and described extensively in previous literature. Interruption of the CD40/CD40L signal causes hyper-IgM (HIGM) syndrome, which has been classified and recognized as a group of rare inherited immune deficiency disorders. Defects in CD40 and CD40L interactions or in downstream signaling molecules, including activation-induced cytidine deaminase, uracyl-DNA-glycosylase, NF-κB and DNA repair enzymes, result in an increased level of serum IgM and a significantly decreased or absent level of IgA, IgG and IgE that is accompanied by severe recurrent infections and autoimmune diseases...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/29114388/epistatic-interactions-between-mutations-of-taci-tnfrsf13b-and-tcf3-result-in-a-severe-primary-immunodeficiency-disorder-and-systemic-lupus-erythematosus
#2
Rohan Ameratunga, Wikke Koopmans, See-Tarn Woon, Euphemia Leung, Klaus Lehnert, Charlotte A Slade, Jessica C Tempany, Anselm Enders, Richard Steele, Peter Browett, Philip D Hodgkin, Vanessa L Bryant
Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies where monogenetic causes account for only a fraction of cases. On this evidence, CVID is potentially polygenic and epistatic although there are, as yet, no examples to support this hypothesis. We have identified a non-consanguineous family, who carry the C104R (c.310T>C) mutation of the Transmembrane Activator Calcium-modulator and cyclophilin ligand Interactor (TACI, TNFRSF13B) gene. Variants in TNFRSF13B/TACI are identified in up to 10% of CVID patients, and are associated with, but not solely causative of CVID...
October 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29113450/physiological-significance-of-plant-peroxiredoxins-prxs-and-the-structure-related-and-multi-functional-biochemistry-of-prx1
#3
Eun Seon Lee, Chang Ho Kang, Joung Hun Park, Sang Yeol Lee
<b><i>Significance:</i></b> Sessile plants respond to oxidative stress caused by internal and external stimuli by producing diverse forms of enzymatic and non-enzymatic antioxidant molecules. Peroxiredoxins (Prxs) in plants, including the Prx1, Prx5, Prx6, and PrxQ isoforms, constitute a family of antioxidant enzymes and play important functions in cells. Each Prx localizes to a specific subcellular compartment and has a distinct function in the control of plant growth, development, cellular metabolism, and various aspects of defense signaling...
November 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29109730/t-follicular-helper-cells-and-b-cell-dysfunction-in-aging-and-hiv-1-infection
#4
REVIEW
Suresh Pallikkuth, Lesley de Armas, Stefano Rinaldi, Savita Pahwa
T follicular helper (Tfh) cells are a subset of CD4 T cells that provide critical signals to antigen-primed B cells in germinal centers to undergo proliferation, isotype switching, and somatic hypermutation to generate long-lived plasma cells and memory B cells during an immune response. The quantity and quality of Tfh cells therefore must be tightly controlled to prevent immune dysfunction in the form of autoimmunity and, on the other hand, immune deficiency. Both Tfh and B cell perturbations appear during HIV infection resulting in impaired antibody responses to vaccines such as seasonal trivalent influenza vaccine, also seen in biologic aging...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29045049/germinal-center-b-cells-are-essential-for-collagen-induced-arthritis
#5
Albert Dahdah, Katrin Habir, Kutty Selva Nandakumar, Amit Saxena, Bingze Xu, Rikard Holmdahl, Stephen Malin
OBJECTIVE: Rheumatoid arthritis (RA) is considered a prototypical autoimmune disorder. Several mechanisms have been proposed for the known pathological function of B cells in RA, including antigen presentation, cytokine secretion and humoral immunity. METHODS: To address the function of B lymphocytes in experimental arthritis, we mapped the adaptive immune response following collagen-induced arthritis (CIA). We subsequently followed these responses and disease outcomes in novel genetically modified mouse strains that lack mature B cells or germinal center functionality in a B cell-intrinsic manner on a CIA MHC-II susceptible background...
October 17, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28965920/selection-and-validation-of-antibody-clones-against-igg-and-iga-subclasses-in-switched-memory-b-cells-and-plasma-cells
#6
Elena Blanco, Martin Perez-Andres, Luzalba Sanoja-Flores, Marjolein Wentink, Ondrej Pelak, Marta Martín-Ayuso, Georgiana Grigore, Juan Torres-Canizales, Eduardo López-Granados, Tomas Kalina, Mirjam van der Burg, Sonia Arriba-Méndez, Santiago Santa Cruz, Noemí Puig, Jacques J M van Dongen, Alberto Orfao
The clinical value of assessing immunoglobulin (Ig)G and IgA subclasses in addition to the isotypes of soluble Igs in serum has been well established. >20years ago, the International Union of Immunological Societies and the World Health Organization performed collaborative studies in order to validate antibody (Ab) clones for the detection of IgG and IgA subclasses for a broad range of laboratory assays, except for flow cytometry. Here we analyzed the performance of commercially available Ab clones to detect IgG and IgA subclasses in memory B-cells and plasma cells (PCs) by flow cytometry...
September 28, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28950009/timing-of-the-human-prenatal-antibody-response-to-plasmodium-falciparum-antigens
#7
Samuel Tassi Yunga, Alexander K Kayatani, Josephine Fogako, Robert J I Leke, Rose G F Leke, Diane W Taylor
Plasmodium falciparum (Pf)-specific T- and B-cell responses may be present at birth; however, when during fetal development antibodies are produced is unknown. Accordingly, cord blood samples from 232 preterm (20-37 weeks of gestation) and 450 term (≥37 weeks) babies were screened for IgM to Pf blood-stage antigens MSP1, MSP2, AMA1, EBA175 and RESA. Overall, 25% [95% CI = 22-28%] of the 682 newborns were positive for IgM to ≥1 Pf antigens with the earliest response occurring at 22 weeks. Interestingly, the odds of being positive for cord blood Pf IgM decreased with gestational age (adjusted OR [95% CI] at 20-31 weeks = 2...
2017: PloS One
https://www.readbyqxmd.com/read/28931676/protective-humoral-immunity-in-the-central-nervous-system-requires-peripheral-cd19-dependent-germinal-center-formation-following-coronavirus-encephalomyelitis
#8
Jeffrey R Atkinson, Cornelia C Bergmann
B cell subsets with phenotypes characteristic of naive, non-isotype-switched, memory (Bmem) cells and antibody-secreting cells (ASC) accumulate in various models of central nervous system (CNS) inflammation, including viral encephalomyelitis. During neurotropic coronavirus JHMV infection, infiltration of protective ASC occurs after T cell-mediated viral control and is preceded by accumulation of non-isotype-switched IgD(+) and IgM(+) B cells. However, the contribution of peripheral activation events in cervical lymph nodes (CLN) to driving humoral immune responses in the infected CNS is poorly defined...
December 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28928744/ccctc-binding-factor-locks-premature-igh-germline-transcription-and-restrains-class-switch-recombination
#9
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/28928405/nanopore-extended-field-effect-transistor-for-selective-single-molecule-biosensing
#10
Ren Ren, Yanjun Zhang, Binoy Paulose Nadappuram, Bernice Akpinar, David Klenerman, Aleksandar P Ivanov, Joshua B Edel, Yuri Korchev
There has been a significant drive to deliver nanotechnological solutions to biosensing, yet there remains an unmet need in the development of biosensors that are affordable, integrated, fast, capable of multiplexed detection, and offer high selectivity for trace analyte detection in biological fluids. Herein, some of these challenges are addressed by designing a new class of nanoscale sensors dubbed nanopore extended field-effect transistor (nexFET) that combine the advantages of nanopore single-molecule sensing, field-effect transistors, and recognition chemistry...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28923960/igh-isotype-specific-b-cell-receptor-expression-influences-b-cell-fate
#11
Pei Tong, Alessandra Granato, Teng Zuo, Neha Chaudhary, Adam Zuiani, Seung Seok Han, Rakesh Donthula, Akritee Shrestha, Debattama Sen, Jennifer M Magee, Michael P Gallagher, Cees E van der Poel, Michael C Carroll, Duane R Wesemann
Ig heavy chain (IgH) isotypes (e.g., IgM, IgG, and IgE) are generated as secreted/soluble antibodies (sIg) or as membrane-bound (mIg) B cell receptors (BCRs) through alternative RNA splicing. IgH isotype dictates soluble antibody function, but how mIg isotype influences B cell behavior is not well defined. We examined IgH isotype-specific BCR function by analyzing naturally switched B cells from wild-type mice, as well as by engineering polyclonal Ighγ1/γ1 and Ighε/ε mice, which initially produce IgG1 or IgE from their respective native genomic configurations...
October 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28911876/immunoglobulin-isotype-switching-of-antibodies-to-vimentin-is-associated-with-development-of-transplant-glomerulopathy-following-human-renal-transplantation
#12
Muthukumar Gunasekaran, Thin Thin Maw, Rowena Delos Santos, Surendra Shenoy, Jason Wellen, T Mohanakumar
BACKGROUND: Immune responses to tissue-restricted self-antigens are thought to play a role in chronic rejection after solid organ transplantation. De novo development of antibodies (Abs) to vimentin have been reported to be associated with interstitial fibrosis/tubular atrophy after kidney transplant, and it has been suggested that immunoglobulin isotype switching of Abs to vimentin may occur during this process. We aimed to determine the correlation between immunoglobulin isotype switching of Abs to vimentin and development of transplant glomerulopathy (TG) after kidney transplant, and to determine whether citrullinated modification of vimentin is required for de novo anti-vimentin development...
September 11, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28886236/waldenstr%C3%A3-m-s-macroglobulinemia-two-malignant-clones-in-a-monoclonal-disease-molecular-background-and-clinical-reflection
#13
REVIEW
Kateřina Growková, Elena Kryukova, Zuzana Kufová, Jana Filipová, Tereza Ševčíková, Lucie Říhová, Michal Kaščák, Fedor Kryukov, Roman Hájek
Waldenström's macroglobulinemia (WM) is a complex disease characterized by apparent morphological heterogeneity within the malignant clonal cells representing a continuum of small lymphocytes, plasmacytoid lymphocytes, and plasma cells. At the molecular level, the neoplastic B cell-derived clone has undergone somatic hypermutation, but not isotype switching, and retains the capability of plasmacytic differentiation. Although by classical definition, WM is formed by monoclonal expansion, long-lived clonal B lymphocytes are of heterogeneous origin...
September 8, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28881401/generation-of-t-follicular-helper-cells-in%C3%A2-vitro-requirement-for-b-cell-receptor-cross-linking-and-cognate-b-and-t-cell-interaction
#14
Anne Kolenbrander, Bastian Grewe, David Nemazee, Klaus Überla, Vladimir Temchura
The minimum requirements for in vitro modelling of natural CD4(+) T-cell differentiation into T follicular helper (Tfh) cells are still under investigation. We co-cultured wild-type and T-cell receptor (TCR) transgenic CD4(+) T cells from naive mice with dendritic cells and B-cell receptor (BCR) transgenic B cells in the presence of HIV-derived virus-like particles containing matched B-cell and T-cell epitopes. This co-culturing induced co-expression of Tfh-master regulator transcription factor BCL-6 and CXCR5 in up to 10% of the wild-type and up to 40% of the TCR-transgenic CD4(+) T cells...
September 7, 2017: Immunology
https://www.readbyqxmd.com/read/28879521/fcrla-a-resident-endoplasmic-reticulum-protein-that-associates-with-multiple-immunoglobulin-isotypes-in-b-lineage-cells
#15
Tessa E Blackburn, Teresa Santiago, Peter D Burrows
FCRLA is homologous to receptors for the Fc portion of IgG (FcγR) and is located in the same region of human chromosome one, but has several unusual and unique features. It is a soluble resident ER protein retained in this organelle by unknown mechanisms involving the N-terminal domain, a disordered domain with three Cys residues in close proximity in the human protein. Unlike the FcγRs, FCRLA is not glycosylated and has no transmembrane region. FCRLA is included in this CTMI volume on IgM-binding proteins because it binds IgM in the ER, but quite surprisingly, given the isotype-restricted ligand specificity of the other FcRs, it also binds all other Ig isotypes so far tested, IgG and IgA...
September 7, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28876451/selective-hdac6-inhibition-decreases-early-stage-of-lupus-nephritis-by-downregulating-both-innate-and-adaptive-immune-responses
#16
Jingjing Ren, Xiaofeng Liao, Miranda D Vieson, Miao Chen, Reilly Scott, Jillian Kazmierczak, Xin M Luo, Christopher M Reilly
We have previously demonstrated that HDAC6 expression is increased in animal models of systemic lupus erythematosus (SLE) and that inhibition of HDAC6 decreased disease. In our current studies, we tested if an orally active selective HDAC6 inhibitor would decrease disease pathogenesis in a lupus mouse model with established early disease. Additionally, we sought to delineate the cellular and molecular mechanism(s) of action of a selective HDAC6 inhibitor in SLE. We treated 20-week-old (early-disease) NZB/W F1 female mice with two different doses of the selective HDAC6 inhibitor (ACY-738) for five weeks...
September 6, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28838616/molecular-analysis-of-immunoglobulin-variable-genes-supports-a-germinal-center-experienced-normal-counterpart-in-primary-cutaneous-diffuse-large-b-cell-lymphoma-leg-type
#17
Anne Pham-Ledard, Martina Prochazkova-Carlotti, Mélanie Deveza, Marie-Pierre Laforet, Marie Beylot-Barry, Béatrice Vergier, Marie Parrens, Jean Feuillard, Jean-Philippe Merlio, Nathalie Gachard
BACKGROUND: Immunophenotype of primary cutaneous diffuse large B-cell lymphoma, leg-type (PCLBCL-LT) suggests a germinal center-experienced B lymphocyte (BCL2+ MUM1+ BCL6+/-). OBJECTIVES: As maturation history of B-cell is "imprinted" during B-cell development on the immunoglobulin gene sequence, we studied the structure and sequence of the variable part of the genes (IGHV, IGLV, IGKV), immunoglobulin surface expression and features of class switching in order to determine the PCLBCL-LT cell of origin...
July 26, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28832951/comparative-analysis-of-plant-produced-recombinant-dimeric-iga-against-cell-wall-%C3%AE-glucan-of-pathogenic-fungi
#18
COMPARATIVE STUDY
Cristina Capodicasa, Marcello Catellani, Ilaria Moscetti, Carla Bromuro, Paola Chiani, Antonella Torosantucci, Eugenio Benvenuto
Immunoglobulins A (IgA) are crucially involved in protection of human mucosal surfaces from microbial pathogens. In this work, we devised and expressed in plants recombinant chimeric antifungal antibodies (Abs) of isotype A (IgA1, IgA2, and scFvFcA1), derived from a murine mAb directed to the fungal cell wall polysaccharide β-glucan which had proven able to confer protection against multiple pathogenic fungi. All recombinant IgA (rIgA) were expressed and correctly assembled in dimeric form in plants and evaluated for yield, antigen-binding efficiency and antifungal properties in vitro, in comparison with a chimeric IgG1 version...
December 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28762497/t-cell-dependent-antigen-adjuvanted-with-dotap-cpg-b-but-not-dotap-cpg-a-induces-robust-germinal-center-responses-and-high-affinity-antibodies-in-mice
#19
Munir Akkaya, Billur Akkaya, Patrick W Sheehan, Pietro Miozzo, Mirna Pena, Chen-Feng Qi, Javier Manzella-Lapeira, Silvia Bolland, Susan K Pierce
The development of vaccines for infectious diseases for which we currently have none, including HIV, will likely require the use of adjuvants that strongly promote germinal center responses and somatic hypermutation to produce broadly neutralizing antibodies. Here we compared the outcome of immunization with the T-cell dependent antigen, NP-conjugated to chicken gamma globulin (NP-CGG) adjuvanted with the toll-like receptor 9 (TLR9) ligands, CpG-A or CpG-B, alone or conjugated with the cationic lipid carrier, DOTAP...
November 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28746783/cd73-expression-identifies-a-subset-of-igm-antigen-experienced-cells-with-memory-attributes-that-is-t-cell-and-cd40-signalling-dependent
#20
Lucas D'Souza, Sneh Lata Gupta, Vineeta Bal, Satyajit Rath, Anna George
B-cell memory was long characterized as isotype-switched, somatically mutated and germinal centre (GC)-derived. However, it is now clear that the memory pool is a complex mixture that includes unswitched and unmutated cells. Further, expression of CD73, CD80 and CD273 has allowed the categorization of B-cell memory into multiple subsets, with combinatorial expression of the markers increasing with GC progression, isotype-switching and acquisition of somatic mutations. We have extended these findings to determine whether these markers can be used to identify IgM memory phenotypically as arising from T-dependent versus T-independent responses...
December 2017: Immunology
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