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Isotype switching

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https://www.readbyqxmd.com/read/28333576/epstein-barr-virus-lytic-reactivation-activates-b-cells-polyclonally-and-induces-activation-induced-cytidine-deaminase-expression-a-mechanism-underlying-autoimmunity-and-its-contribution-to-graves-disease
#1
Keiko Nagata, Keisuke Kumata, Yuji Nakayama, Yukio Satoh, Hirotsugu Sugihara, Sayuri Hara, Michiko Matsushita, Satoshi Kuwamoto, Masako Kato, Ichiro Murakami, Kazuhiko Hayashi
Graves' disease is an autoimmune disease that results in and is the most common cause of hyperthyroidism, and the reactivation of persisting Epstein-Barr virus (EBV) in B lymphocytes induces the differentiation of host B cells into plasma cells. We previously reported that some EBV-infected B cells had thyrotropin receptor antibodies (TRAbs) as surface immunoglobulins (Igs), and EBV reactivation induced these TRAb+EBV+ cells to produce TRAbs. EBV reactivation induces Ig production from host B cells. The purpose of the present study was to examine total Ig productions from B cell culture fluids and to detect activation-induced cytidine deaminase (AID), nuclear factor kappa B (NF-κB), and EBV latent membrane protein (LMP) 1 in culture B cells during EBV reactivation induction and then we discussed the mechanisms of EBV reactivation-induced Ig production in relation to autoimmunity...
March 23, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28302908/tubulin-isotype-substitution-revealed-that-isotype-composition-modulates-microtubule-dynamics-in-c-elegans-embryos
#2
Yu Honda, Kenta Tsuchiya, Eisuke Sumiyoshi, Nami Haruta, Asako Sugimoto
Microtubules (MTs) are polymers composed of α- and β-tubulin heterodimers, which are generally encoded by multiple gene loci. Despite implications of distinct properties of isotypes, how they contribute to diverse MT dynamics in vivo remains unclear. Here, using genome editing and RNAi depletion of tubulin isotypes, we demonstrate that four tubulin isotypes (hereafter α1, α2, β1 and β2) cooperatively confer distinct MT properties in Caenorhabditis elegans early embryos. GFP insertion into each isotype locus reveals their distinct expression levels and MT incorporation rates...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28286158/smith-magenis-syndrome-patients-often-display-antibody-deficiency-but-not-other-immune-pathologies
#3
Tiffany Perkins, Jacob M Rosenberg, Carole Le Coz, Joseph T Alaimo, Melissa Trofa, Sureni V Mullegama, Richard J Antaya, Soma Jyonouchi, Sarah H Elsea, Paul J Utz, Eric Meffre, Neil Romberg
BACKGROUND: Smith-Magenis syndrome (SMS) is a complex neurobehavioral disorder associated with recurrent otitis. Most SMS cases result from heterozygous interstitial chromosome 17p11.2 deletions that encompass not only the intellectual disability gene retinoic acid-induced 1 but also other genes associated with immunodeficiency, autoimmunity, and/or malignancy. OBJECTIVES: The goals of this study were to describe the immunological consequence of 17p11.2 deletions by determining the prevalence of immunological diseases in subjects with SMS and by assessing their immune systems via laboratory methods...
March 9, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28222195/autoantibodies-against-mono-and-tri-methylated-lysine-display-similar-but-also-distinctive-characteristics
#4
Zhiqiang Wang, Younan Ma, Fan Liu, Linjie Chen, Ruitong Gao, Wei Zhang
Autoantibodies can be either harmful or beneficial to the body. The beneficial autoantibodies play important roles in immunosurveillance, clearance of body waste and maintenance of immune homeostasis. Despite their importance, however, people's knowledge on the protective autoantibodies is still very limited. In the current study, we examined two autoantibodies that recognized epitopes with only one amino acid. One was against mono-methylated lysine (Kme) and the other was against tri-methylated lysine (Kme3)...
2017: PloS One
https://www.readbyqxmd.com/read/28154564/immunization-of-newborn-mice-accelerates-the-architectural-maturation-of-lymph-nodes-but-aid-dependent-igg-responses-are-still-delayed-compared-to-the-adult
#5
Rosario Munguía-Fuentes, Juan Carlos Yam-Puc, Aarón Silva-Sánchez, Edith Marcial-Juárez, Isis Amara Gallegos-Hernández, Juana Calderón-Amador, Troy D Randall, Leopoldo Flores-Romo
Lymph nodes (LNs) have evolved to maximize antigen (Ag) collection and presentation as well as lymphocyte proliferation and differentiation-processes that are spatially regulated by stromal cell subsets, including fibroblastic reticular cells (FRCs) and follicular dendritic cells (FDCs). Here, we showed that naïve neonatal mice have poorly organized LNs with few B and T cells and undetectable FDCs, whereas adult LNs have numerous B cells and large FDC networks. Interestingly, immunization on the day of birth accelerated B cell accumulation and T cell recruitment into follicles as well as FDC maturation and FRC organization in neonatal LNs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28137874/igd-class-switching-is-initiated-by-microbiota-and-limited-to-mucosa-associated-lymphoid-tissue-in-mice
#6
Jin Huk Choi, Kuan-Wen Wang, Duanwu Zhang, Xiaowei Zhan, Tao Wang, Chun-Hui Bu, Cassie L Behrendt, Ming Zeng, Ying Wang, Takuma Misawa, Xiaohong Li, Miao Tang, Xiaoming Zhan, Lindsay Scott, Sara Hildebrand, Anne R Murray, Eva Marie Y Moresco, Lora V Hooper, Bruce Beutler
Class-switch recombination (CSR) alters the Ig isotype to diversify antibody effector functions. IgD CSR is a rare event, and its regulation is poorly understood. We report that deficiency of 53BP1, a DNA damage-response protein, caused age-dependent overproduction of secreted IgD resulting from increased IgD CSR exclusively within B cells of mucosa-associated lymphoid tissues. IgD overproduction was dependent on activation-induced cytidine deaminase, hematopoietic MyD88 expression, and an intact microbiome, against which circulating IgD, but not IgM, was reactive...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28125732/dysregulation-of-systemic-and-mucosal-humoral-responses-to-microbial-and-food-antigens-as-a-factor-contributing-to-microbial-translocation-and-chronic-inflammation-in-hiv-1-infection
#7
Zdenek Hel, Jun Xu, Warren L Denning, E Scott Helton, Richard P H Huijbregts, Sonya L Heath, E Turner Overton, Benjamin S Christmann, Charles O Elson, Paul A Goepfert, Jiri Mestecky
HIV-1 infection is associated with an early and profound depletion of mucosal memory CD4+ T cells, a population that plays an indispensable role in the regulation of isotype switching and transepithelial transport of antibodies. In this study, we addressed whether the depletion of CD4+ T cell in HIV-1-infected individuals results in altered humoral responses specific to antigens encountered at mucosal surfaces. Comprehensive protein microarray of systemic humoral responses to intestinal microbiota demonstrated reduced IgG responses to antigens derived from Proteobacteria and Firmicutes but not Bacteroidetes...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28115508/eye-drop-inoculation-leads-to-sublethal-leptospirosis-in-mice
#8
Joseph Pierce Sullivan, Nisha Nair, Hari-Hara Potula, Maria Gomes-Solecki
Leptospirosis is potentially a fatal zoonosis acquired by contact of skin and mucosal surfaces with soil and water contaminated with infected urine. We analyzed the outcome of infection of C3H-HeJ mice with Leptospira interrogans serovar Copenhageni, using an enzootic mode of transmission, the conjunctival route. Infection led to weight loss and L. interrogans dissemination from blood to urine. However, the sequence of these events occurred later and were not as clearly separated in time given that spirochete detection overlapped in both tissues...
January 23, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28107431/characterization-of-a-broadly-reactive-anti-cd40-agonistic-monoclonal-antibody-for-potential-use-as-an-adjuvant
#9
Cameron Martin, Suryakant D Waghela, Shehnaz Lokhandwala, Andy Ambrus, Jocelyn Bray, Christina Vuong, Vanitha Vinodkumar, Paul J Dominowski, Sharath Rai, Duncan Mwangi, Dennis L Foss, Waithaka Mwangi
Lack of safe and effective adjuvants is a major hindrance to the development of efficacious vaccines. Signaling via CD40 pathway leads to enhanced antigen processing and presentation, nitric oxide expression, pro-inflammatory cytokine expression by antigen presenting cells, and stimulation of B-cells to undergo somatic hypermutation, immunoglobulin class switching, and proliferation. Agonistic anti-CD40 antibodies have shown promising adjuvant qualities in human and mouse vaccine studies. An anti-CD40 monoclonal antibody (mAb), designated 2E4E4, was identified and shown to have strong agonistic effects on primary cells from multiple livestock species...
2017: PloS One
https://www.readbyqxmd.com/read/28095113/quantitative-analysis-of-cell-surface-antigen-antibody-interaction-using-gaussia-princeps-luciferase-antibody-fusion-proteins
#10
Juliane Kums, Johannes Nelke, Benedikt Rüth, Viktoria Schäfer, Daniela Siegmund, Harald Wajant
Cell surface antigen-specific antibodies are of substantial diagnostic and therapeutic importance. The binding properties of such antibodies are usually evaluated by cell-free assays, in particular surface plasmon resonance (SPR) analysis, or flow cytometry. SPR analyses allow the detailed quantitative and dynamic evaluation of the binding properties of antibodies, but need purified, typically recombinantly produced antigens. It can, however, be difficult to produce the required antigen. Furthermore, cellular factors influencing the antigen-antibody interaction are not considered by this method...
January 17, 2017: MAbs
https://www.readbyqxmd.com/read/28093652/structural-basis-for-the-isotype-specific-interactions-of-ferredoxin-and-ferredoxin-nadp-oxidoreductase-an-evolutionary-switch-between-photosynthetic-and-heterotrophic-assimilation
#11
Fumio Shinohara, Genji Kurisu, Guy Hanke, Caroline Bowsher, Toshiharu Hase, Yoko Kimata-Ariga
In higher plants, ferredoxin (Fd) and ferredoxin-NADP(+) reductase (FNR) are each present as distinct isoproteins of photosynthetic type (leaf type) and non-photosynthetic type (root type). Root-type Fd and FNR are considered to facilitate the electron transfer from NADPH to Fd in the direction opposite to that occurring in the photosynthetic processes. We previously reported the crystal structure of the electron transfer complex between maize leaf FNR and Fd (leaf FNR:Fd complex), providing insights into the molecular interactions of the two proteins...
January 16, 2017: Photosynthesis Research
https://www.readbyqxmd.com/read/28086979/b-cell-repertoires-in-hla-sensitized-kidney-transplant-candidates-undergoing-desensitization-therapy
#12
John F Beausang, H Christina Fan, Rene Sit, Maria U Hutchins, Kshama Jirage, Rachael Curtis, Edward Hutchins, Stephen R Quake, Julie M Yabu
BACKGROUND: Kidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy. METHODS: We developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels...
January 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28065739/r-loop-depletion-by-over-expressed-rnase-h1-in-mouse-b-cells-increases-activation-induced-deaminase-access-to-the-transcribed-strand-without-altering-frequency-of-isotype-switching
#13
Robert W Maul, Hyongi Chon, Kiran Sakhuja, Susana M Cerritelli, Lina A Gugliotti, Patricia J Gearhart, Robert J Crouch
R-loops, three-strand structures consisting of mRNA hybridized to the complementary DNA and a single-stranded DNA loop, are formed in switch regions on the heavy-chain immunoglobulin locus. To determine if R-loops have a direct effect on any of the steps involved in isotype switching, we generated a transgenic mouse that over-expressed RNase H1, an enzyme that cleaves the RNA of RNA/DNA hybrids in B cells. R-loops in the switch μ region were depleted by 70% in ex vivo activated splenic B cells. Frequencies of isotype switching to IgG1, IgG2b, IgG2c, and IgG3 were the same as C57BL/6 control cells...
January 6, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28053999/b-cell-populations-discriminate-between-pediatric-and-adult-onset-multiple-sclerosis
#14
Alexander Schwarz, Bettina Balint, Mirjam Korporal-Kuhnke, Sven Jarius, Kathrin von Engelhardt, Alexandra Fürwentsches, Cornelia Bussmann, Friedrich Ebinger, Brigitte Wildemann, Jürgen Haas
OBJECTIVE: To comparatively assess the B-cell composition in blood and CSF of patients with pediatric-onset multiple sclerosis (pedMS) and adult-onset multiple sclerosis (adMS). METHODS: In this cross-sectional study, we obtained blood and CSF samples from 25 patients with pedMS (8-18 years) and 40 patients with adMS (23-65 years) and blood specimens from 66 controls (1-55 years). By using multicolor flow cytometry, we identified naive, transitional, isotype class-switched memory, nonswitched memory, and double-negative memory B-cell subsets as well as plasmablasts (PB) and terminally differentiated plasma cells (PC)...
January 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28011866/the-aryl-hydrocarbon-receptor-controls-cell-fate-decisions-in-b-cells
#15
Bharat Vaidyanathan, Ashutosh Chaudhry, William T Yewdell, Davide Angeletti, Wei-Feng Yen, Adam K Wheatley, Christopher A Bradfield, Adrian B McDermott, Jonathan W Yewdell, Alexander Y Rudensky, Jayanta Chaudhuri
Generation of cellular heterogeneity is an essential feature of the adaptive immune system. This is best exemplified during humoral immune response when an expanding B cell clone assumes multiple cell fates, including class-switched B cells, antibody-secreting plasma cells, and memory B cells. Although each cell type is essential for immunity, their generation must be exquisitely controlled because a class-switched B cell cannot revert back to the parent isotype, and a terminally differentiated plasma cell cannot contribute to the memory pool...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27974207/dna-replication-origins-in-immunoglobulin-switch-regions-regulate-class-switch-recombination-in-an-r-loop-dependent-manner
#16
Eva-Maria Wiedemann, Mihaela Peycheva, Rushad Pavri
Class switch recombination (CSR) at the immunoglobulin heavy chain (IgH) locus generates antibody isotypes. CSR depends on double-strand breaks (DSBs) induced by activation-induced cytidine deaminase (AID). Although DSB formation and repair machineries are active in G1 phase, efficient CSR is dependent on cell proliferation and S phase entry; however, the underlying mechanisms are obscure. Here, we show that efficient CSR requires the replicative helicase, the Mcm complex. Mcm proteins are enriched at IgH switch regions during CSR, leading to assembly of facultative replication origins that require Mcm helicase function for productive CSR...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27940658/cutting-edge-il-10-is-essential-for-the-generation-of-germinal-center-b-cell-responses-and-anti-plasmodium-humoral-immunity
#17
Jenna J Guthmiller, Amy C Graham, Ryan A Zander, Rosemary L Pope, Noah S Butler
IL-10 is a pleiotropic cytokine expressed during malaria, a disease characterized by short-lived, parasite-specific Ab responses. The role of IL-10 in regulating B cell responses during malaria is not known. In this study we report that IL-10 is essential for anti-Plasmodium humoral immunity. We identify that germinal center (GC) B cell reactions, isotype-switched Ab responses, parasite control, and host survival require B cell-intrinsic IL-10 signaling. IL-10 also indirectly supports humoral immunity by suppressing excessive IFN-γ, which induces T-bet expression in B cells...
January 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27924814/mature-igm-expressing-plasma-cells-sense-antigen-and-develop-competence-for-cytokine-production-upon-antigenic-challenge
#18
Pascal Blanc, Ludovic Moro-Sibilot, Lucas Barthly, Ferdinand Jagot, Sébastien This, Simon de Bernard, Laurent Buffat, Sébastien Dussurgey, Renaud Colisson, Elias Hobeika, Thierry Fest, Morgan Taillardet, Olivier Thaunat, Antoine Sicard, Paul Mondière, Laurent Genestier, Stephen L Nutt, Thierry Defrance
Dogma holds that plasma cells, as opposed to B cells, cannot bind antigen because they have switched from expression of membrane-bound immunoglobulins (Ig) that constitute the B-cell receptor (BCR) to production of the secreted form of immunoglobulins. Here we compare the phenotypical and functional attributes of plasma cells generated by the T-cell-dependent and T-cell-independent forms of the hapten NP. We show that the nature of the secreted Ig isotype, rather than the chemical structure of the immunizing antigen, defines two functionally distinct populations of plasma cells...
December 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27919754/neutralization-takes-precedence-over-igg-or-iga-isotype-related-functions-in-mucosal-hiv-1-antibody-mediated-protection
#19
Rena D Astronomo, Sampa Santra, Lamar Ballweber-Fleming, Katharine G Westerberg, Linh Mach, Tiffany Hensley-McBain, Laura Sutherland, Benjamin Mildenberg, Georgeanna Morton, Nicole L Yates, Gregory J Mize, Justin Pollara, Florian Hladik, Christina Ochsenbauer, Thomas N Denny, Ranjit Warrier, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Jaranit Kaewkungwal, Guido Ferrari, George M Shaw, Shi-Mao Xia, Hua-Xin Liao, David C Montefiori, Georgia D Tomaras, Barton F Haynes, Juliana M McElrath
HIV-1 infection occurs primarily through mucosal transmission. Application of biologically relevant mucosal models can advance understanding of the functional properties of antibodies that mediate HIV protection, thereby guiding antibody-based vaccine development. Here, we employed a human ex vivo vaginal HIV-1 infection model and a rhesus macaque in vivo intrarectal SHIV challenge model to probe the protective capacity of monoclonal broadly-neutralizing (bnAb) and non-neutralizing Abs (nnAbs) that were functionally modified by isotype switching...
2016: EBioMedicine
https://www.readbyqxmd.com/read/27897229/global-gene-regulation-during-activation-of-immunoglobulin-class-switching-in-human-b-cells
#20
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
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