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IgA class switch

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https://www.readbyqxmd.com/read/30356862/marginal-zone-b-cells-are-main-producers-of-igm-in-humans-and-are-reduced-in-patients-with-autoimmune-vasculitis
#1
Daniel Appelgren, Per Eriksson, Jan Ernerudh, Mårten Segelmark
In mice, B1 and marginal zone (MZ) B-cells play an important role in prevention of autoimmunity through production of regulatory cytokines and natural antibodies. There is limited knowledge about the human counterparts of these cells. We therefore investigated functions of MZ-like B-cells and the frequency of circulating MZ-like and B1-like B-cells in healthy controls (HC), as well as in patients with autoimmune vasculitis to learn more about the role of these cells in autoimmune disease. After stimulation with CpG oligodeoxynucleotides (ODN) of class B in vitro , MZ-like B-cells were the main producers of IgM whereas switched memory B-cells primarily produced IgG and IgA...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30352169/b-cells-caught-in-the-act-class-switching-to-iga-in-lung-lymphoid-follicles-in-copd
#2
Jeffrey L Curtis
No abstract text is available yet for this article.
October 23, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/30319630/class-switch-recombination-csr-hyper-igm-higm-syndromes-and-phosphoinositide-3-kinase-pi3k-defects
#3
REVIEW
Rekha D Jhamnani, Cristiane J Nunes-Santos, Jenna Bergerson, Sergio D Rosenzweig
Antibody production and function represent an essential part of the immune response, particularly in fighting bacterial and viral infections. Multiple immunological phenotypes can result in dysregulation of the immune system humoral compartment, including class-switch recombination (CSR) defects associated with hyper-IgM (HIGM) syndromes. The CSR/HIGM syndromes are defined by the presence of normal or elevated plasma IgM levels in the context of low levels of switched IgG, IgA, and IgE isotypes. Recently described autosomal dominant gain-of-function (GOF) mutations in PIK3CD and PIK3R1 cause combined immunodeficiencies that can also present as CSR/HIGM defects...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30181913/murine-%C3%AE-%C3%AE-t-cells-render-b-cells-refractory-to-commitment-of-iga-isotype-switching
#4
Hye-Ju Han, Young-Saeng Jang, Goo-Young Seo, Sung-Gyoo Park, Seung Goo Kang, Sung-Il Yoon, Hyun-Jeong Ko, Geun-Shik Lee, Pyeung-Hyeun Kim
γδ T cells are abundant in the gut mucosa and play an important role in adaptive immunity as well as innate immunity. Although γδ T cells are supposed to be associated with the enhancement of Ab production, the status of γδ T cells, particularly in the synthesis of IgA isotype, remains unclear. We compared Ig expression in T cell receptor delta chain deficient (TCRδ-/- ) mice with wild-type mice. The amount of IgA in fecal pellets was substantially elevated in TCRδ-/- mice. This was paralleled by an increase in surface IgA expression and total IgA production by Peyer's patches (PPs) and mesenteric lymph node (MLN) cells...
August 2018: Immune Network
https://www.readbyqxmd.com/read/30081731/genetic-analysis-of-patients-with-two-different-types-of-hyper-igm-syndrome
#5
Zahra Alizadeh, Marzieh Mazinani, Masoud Houshmand, Leila Shakerian, Maryam Nourizadeh, Zahra Pourpak, Mohammad Reza Fazlollahi
BACKGROUND: Hyper IgM Syndrome (HIGM) is a rare primary immunodeficiency in which impairment of class switching recombination (CSR) and somatic hyper-mutation (SHM) leads to recurrent infections. OBJECTIVES: The aim of this study is to report the clinical and genetic features of six Iranian HIGM patients. METHODS: Six patients, who suspected to have HIGM based on two clinical findings, including recurrent infections and low levels of IgG and IgA and normal or elevated levels of IgM, were entered this study to undergo genetic studies...
August 6, 2018: Immunological Investigations
https://www.readbyqxmd.com/read/30013564/no-overt-clinical-immunodeficiency-despite-immune-biological-abnormalities-in-patients-with-constitutional-mismatch-repair-deficiency
#6
Victoria K Tesch, Hanna IJspeert, Andrea Raicht, Daniel Rueda, Nerea Dominguez-Pinilla, Luis M Allende, Chrystelle Colas, Thorsten Rosenbaum, Denisa Ilencikova, Hagit N Baris, Michaela H M Nathrath, Manon Suerink, Danuta Januszkiewicz-Lewandowska, Iman Ragab, Amedeo A Azizi, Soeren S Wenzel, Johannes Zschocke, Wolfgang Schwinger, Matthias Kloor, Claudia Blattmann, Laurence Brugieres, Mirjam van der Burg, Katharina Wimmer, Markus G Seidel
Immunoglobulin class-switch recombination (CSR) and somatic hypermutations (SHMs) are prerequisites for antibody and immunoglobulin receptor maturation and adaptive immune diversity. The mismatch repair (MMR) machinery, consisting of homologs of MutSα, MutLα, and MutSβ (MSH2/MSH6, MLH1/PMS2, and MSH2/MSH3, respectively) and other proteins, is involved in CSR, primarily acting as a backup for nonhomologous end-joining repair of activation-induced cytidine deaminase-induced DNA mismatches and, furthermore, in addition to error-prone polymerases, in the repair of SHM-induced DNA breaks...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29907762/duplication-of-a-germline-promoter-downstream-of-the-igh-3-regulatory-region-impairs-class-switch-recombination
#7
Joana M Santos, Fatima-Zohra Braikia, Chloé Oudinet, Dania Haddad, Caroline Conte, Audrey Dauba, Ahmed Amine Khamlichi
During an adaptive immune response, B cells can change their surface immunoglobulins from IgM to IgG, IgE or IgA through a process called class switch recombination (CSR). Switching is preceded by inducible non-coding germline transcription (GLT) of the selected constant gene(s), which is largely controlled by a super-enhancer called the 3' regulatory region (3'RR). Despite intense efforts, the precise mechanisms that regulate GLT are still elusive. In order to gain additional insights into these mechanisms, we analyzed GLT and CSR in mutant B cells carrying a duplication of the promoter of the α constant gene (Iα) downstream of 3'RR...
June 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29887727/heterogeneity-of-memory-marginal-zone-b-cells
#8
Jacobus Hendricks, Nicolaas A Bos, Frans G M Kroese
The marginal zone (MZ) is largely composed of a unique subpopulation of B cells, the so-called MZ-B cells. At a molecular level, memory B cells are characterized by the presence of somatically mutated IGV genes. The earliest studies in the rat have documented the presence of hapten-specific MZ-B cells after immunization in the MZ. This work later received experimental support demonstrating that the IGHV-Cµ transcripts expressed by phenotypically defined splenic MZ-B cells (defined as CD90neg IgMhigh IgDlow B cells) can carry somatic hypermutation...
2018: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/29755476/transitional-b-cells-and-tlr9-responses-are-defective-in-selective-iga-deficiency
#9
Andri L Lemarquis, Helga K Einarsdottir, Rakel N Kristjansdottir, Ingileif Jonsdottir, Bjorn R Ludviksson
Selective IgA deficiency (IgAD) is the most common primary antibody deficiency in the western world with affected individuals suffering from an increased burden of autoimmunity, atopic diseases and infections. It has been shown that IgAD B cells can be induced with germinal center mimicking reactions to produce IgA. However, IgA is the most prevalent antibody in mucosal sites, where antigen-independent responses are important. Much interest has recently focused on the role of TLR9 in both naïve and mature B cell differentiation into IgA secreting plasma cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29746558/anti-citrullinated-protein-antibody-response-after-primary-ebv-infection-in-kidney-transplant-patients
#10
Lianne J N Kraal, Marieke L Nijland, Kristine L Germar, Dominique L P Baeten, Ineke J M Ten Berge, Cynthia M Fehres
Rheumatoid arthritis (RA) is a chronic inflammatory disease of synovial joints, characterized by the presence of the highly disease-specific anti-citrullinated protein antibodies (ACPA) in approximately 70% of patients. Epstein-Barr virus (EBV) has previously been suggested to be involved in the pathophysiology of RA. However, given the high incidence of EBV in the general population and the difficulty of detecting initial infection, providing a direct link between EBV infection and RA development has remained elusive...
2018: PloS One
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...
June 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29664567/memory-control-by-the-b-cell-antigen-receptor
#12
REVIEW
Niklas Engels, Jürgen Wienands
The generation of memory B cells (MBCs) that have undergone immunoglobulin class switching from IgM, which dominates primary antibody responses, to other immunoglobulin isoforms is a hallmark of immune memory. Hence, humoral immunological memory is characterized by the presence of serum immunoglobulins of IgG subtypes known as the γ-globulin fraction of blood plasma proteins. These antibodies reflect the antigen experience of B lymphocytes and their repeated triggering. In fact, efficient protection against a previously encountered pathogen is critically linked to the production of pathogen-specific IgG molecules even in those cases where the primary immune response required cellular immunity, for example, T cell-mediated clearance of intracellular pathogens such as viruses...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29651973/the-clinical-and-immunological-features-of-patients-with-primary-antibody-deficiencies
#13
Gholamreza Azizi, Yasser Bagheri, Marzieh Tavakol, Forough Askarimoghaddam, Kumars Porrostami, Hosein Rafiemanesh, Reza Yazdani, Fatemeh Kiaee, Sima Habibi, Kosar Abouhamzeh, Hamed Mohammadi, Mostafa Qorbani, Hassan Abolhassani, Asghar Aghamohammadi
BACKGROUND: Primary antibody deficiency (PAD) comprises a range of diseases from early to late terminal B cells defects and is associated with the various clinical complications. METHODS: A total of 461 patients (311 males and 150 females) with PADs enrolled in the retrospective cohort study and for all patients' demographic information, clinical records and laboratory data were collected to investigate clinical complications. RESULTS: The most prevalent first presentations of immunodeficiency were respiratory tract infections in 63...
2018: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29618665/b-lymphocytes-confer-immune-tolerance-via-cell-surface-garp-tgf-%C3%AE-complex
#14
Caroline H Wallace, Bill X Wu, Mohammad Salem, Ephraim A Ansa-Addo, Alessandra Metelli, Shaoli Sun, Gary Gilkeson, Mark J Shlomchik, Bei Liu, Zihai Li
GARP, a cell surface docking receptor for binding and activating latent TGF-β, is highly expressed by platelets and activated Tregs. While GARP is implicated in immune invasion in cancer, the roles of the GARP-TGF-β axis in systemic autoimmune diseases are unknown. Although B cells do not express GARP at baseline, we found that the GARP-TGF-β complex is induced on activated human and mouse B cells by ligands for multiple TLRs, including TLR4, TLR7, and TLR9. GARP overexpression on B cells inhibited their proliferation, induced IgA class-switching, and dampened T cell-independent antibody production...
April 5, 2018: JCI Insight
https://www.readbyqxmd.com/read/29567905/diminished-cd40l-expression-on-t-cells-in-a-case-of-disseminated-cryptococcosis
#15
Supreet Kumar Mohanty, Deepshi Thakral, Devika Gupta, Prabin Kumar, Dipendra Kumar Mitra
X-linked hyperimmunoglobulin M (HIGM) syndrome may increase the susceptibility of patients to disseminated cryptococcal infections primarily due to CD40L deficiency that causes defective cross talk between T- and B-cells, thus preventing class switching. In HIGM syndrome, serum IgM levels are elevated with severe reduction in serum immunoglobulin G (IgG) and IgA levels. In addition, the expression of CD40L (CD154) on in vitro-activated T-cells is severely reduced or absent. Here, we describe a rare, and perhaps, the first reported case in India of a 3-year-old male child with X-linked HIGM immunodeficiency syndrome who developed disseminated Cryptococcosis...
January 2018: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29557246/dupilumab-for-treatment-of-atopic-dermatitis
#16
REVIEW
Marlene Seegräber, Jerome Srour, Alexandra Walter, Macarena Knop, Andreas Wollenberg
Dupilumab is a new treatment option for patients with moderate-to-severe atopic dermatitis. It blocks IL-4/IL13-signaling and thereby inhibits receptor signaling downstream the JAK-STAT-pathway. Three of the main disease mechanisms of atopic dermatitis are affected by blocking this pathway; the decrease of skin barrier function, the class switch to IgE and the TH2-differentiation. Areas Covered: Dupilumab showed promising results in clinical trials of phase I-III. Clinical outcome parameters such as SCORAD, EASI, IGA and BSA improved with dupilumab...
May 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29535710/genome-wide-association-study-on-immunoglobulin-g-glycosylation-patterns
#17
Annika Wahl, Erik van den Akker, Lucija Klaric, Jerko Štambuk, Elisa Benedetti, Rosina Plomp, Genadij Razdorov, Irena Trbojević-Akmačić, Joris Deelen, Diana van Heemst, P Eline Slagboom, Frano Vučković, Harald Grallert, Jan Krumsiek, Konstantin Strauch, Annette Peters, Thomas Meitinger, Caroline Hayward, Manfred Wuhrer, Marian Beekman, Gordan Lauc, Christian Gieger
Immunoglobulin G (IgG), a glycoprotein secreted by plasma B-cells, plays a major role in the human adaptive immune response and are associated with a wide range of diseases. Glycosylation of the Fc binding region of IgGs, responsible for the antibody's effector function, is essential for prompting a proper immune response. This study focuses on the general genetic impact on IgG glycosylation as well as corresponding subclass specificities. To identify genetic loci involved in IgG glycosylation, we performed a genome-wide association study (GWAS) on liquid chromatography electrospray mass spectrometry (LC-ESI-MS)-measured IgG glycopeptides of 1,823 individuals in the Cooperative Health Research in the Augsburg Region (KORA F4) study cohort...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29520062/the-h2b-deubiquitinase-usp22-promotes-antibody-class-switch-recombination-by-facilitating-non-homologous-end-joining
#18
Conglei Li, Thergiory Irrazabal, Clare C So, Maribel Berru, Likun Du, Evelyn Lam, Alexanda K Ling, Jennifer L Gommerman, Qiang Pan-Hammarström, Alberto Martin
Class switch recombination (CSR) has a fundamental function during humoral immune response and involves the induction and subsequent repair of DNA breaks in the immunoglobulin (Ig) switch regions. Here we show the role of Usp22, the SAGA complex deubiquitinase that removes ubiquitin from H2B-K120, in the repair of programmed DNA breaks in vivo. Ablation of Usp22 in primary B cells results in defects in γH2AX and impairs the classical non-homologous end joining (c-NHEJ), affecting both V(D)J recombination and CSR...
March 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29511621/robust-dna-repair-in-paxx-deficient-mammalian-cells
#19
Alisa Dewan, Mengtan Xing, Marie Benner Lundbæk, Raquel Gago-Fuentes, Carole Beck, Per Arne Aas, Nina-Beate Liabakk, Siri Sæterstad, Khac Thanh Phong Chau, Bodil Merete Kavli, Valentyn Oksenych
To ensure genome stability, mammalian cells employ several DNA repair pathways. Nonhomologous DNA end joining (NHEJ) is the DNA repair process that fixes double-strand breaks throughout the cell cycle. NHEJ is involved in the development of B and T lymphocytes through its function in V(D)J recombination and class switch recombination (CSR). NHEJ consists of several core and accessory factors, including Ku70, Ku80, XRCC4, DNA ligase 4, DNA-PKcs, Artemis, and XLF. Paralog of XRCC4 and XLF (PAXX) is the recently described accessory NHEJ factor that structurally resembles XRCC4 and XLF and interacts with Ku70/Ku80...
March 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29497996/defective-activation-of-the-mapk-erk-pathway-leading-to-parp1-and-dnmt1-dysregulation-is-a-common-defect-in-iga-nephropathy-and-henoch-sch%C3%A3-nlein-purpura
#20
Annamaria Milillo, Clelia Molinario, Stefano Costanzi, Gisella Vischini, Francesca La Carpia, Francesco La Greca, Donato Rigante, Giovanni Gambaro, Fiorella Gurrieri, Eugenio Sangiorgi
Studies on IgA nephropathy (IgAN) have identified, through GWAS, linkage analysis, and pathway scanning, molecular defects in familial and sporadic IgAN patients. In our previous study, we identified a novel variant in the SPRY2 gene that segregates with the disease in one large family. The functional characterization of this variant led us to discover that the MAPK/ERK pathway was defective not only in this family, but also in two sporadic IgAN patients wild type for SPRY2. In the present study, we have deepened the molecular analysis of the MAPK/ERK pathway and extended our evaluation to a larger cohort of sporadic patients and to one additional family...
October 2018: Journal of Nephrology
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