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Plasmablast

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https://www.readbyqxmd.com/read/29133782/mtor-intersects-antibody-inducing-signals-from-taci-in-marginal-zone-b-cells
#1
Jordi Sintes, Maurizio Gentile, Shuling Zhang, Yolanda Garcia-Carmona, Giuliana Magri, Linda Cassis, Daniel Segura-Garzón, Alessandra Ciociola, Emilie K Grasset, Sabrina Bascones, Laura Comerma, Marc Pybus, David Lligé, Irene Puga, Cindy Gutzeit, Bing He, Wendy DuBois, Marta Crespo, Julio Pascual, Anna Mensa, Juan Ignacio Aróstegui, Manel Juan, Jordi Yagüe, Sergi Serrano, Josep Lloreta, Eric Meffre, Michael Hahne, Charlotte Cunningham-Rundles, Beverly A Mock, Andrea Cerutti
Mechanistic target of rapamycin (mTOR) enhances immunity in addition to orchestrating metabolism. Here we show that mTOR coordinates immunometabolic reconfiguration of marginal zone (MZ) B cells, a pre-activated lymphocyte subset that mounts antibody responses to T-cell-independent antigens through a Toll-like receptor (TLR)-amplified pathway involving transmembrane activator and CAML interactor (TACI). This receptor interacts with mTOR via the TLR adapter MyD88. The resulting mTOR activation instigates MZ B-cell proliferation, immunoglobulin G (IgG) class switching, and plasmablast differentiation through a rapamycin-sensitive pathway that integrates metabolic and antibody-inducing transcription programs, including NF-κB...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29118244/isolation-and-characterization-of-antigen-specific-plasmablasts-using-a-novel-flow-cytometry-based-ig-capture-assay
#2
Christopher L Pinder, Sven Kratochvil, Deniz Cizmeci, Luke Muir, Yanping Guo, Robin J Shattock, Paul F McKay
We report the development of a novel flow cytometry-based Ig capture assay (ICA) for the identification and sorting of individual Ab-secreting cells based on their Ag reactivity. The ICA represents a fast and versatile tool for single-cell sorting of peripheral plasmablasts, streamlining subsequent Ab analysis, and cloning. We demonstrate the utility of the assay by isolating Ag-reactive plasmablasts from cryopreserved PBMC obtained from volunteers vaccinated with a recombinant HIV envelope protein. To show the specificity of the ICA, we produced Ag-specific Abs from these cells and subsequently verified their Ag reactivity via ELISA...
November 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29109124/endogenous-calcitriol-synthesis-controls-the-humoral-ige-response-in-mice
#3
Juliane Lindner, Sebastian Rausch, Sandra Treptow, Kerstin Geldmeyer-Hilt, Tina Krause, René St-Arnaud, Alice Arabian, Andreas Radbruch, Susanne Hartmann, Margitta Worm, Guido Heine
The vitamin D receptor participates in the control of IgE class-switch recombination in B cells. The physiologic vitamin D receptor agonist, 1,25(OH)2D3 (calcitriol), is synthesized by the essential enzyme 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1), which can be expressed by activated immune cells. The role of endogenous calcitriol synthesis for the regulation of IgE has not been proven. In this study, we investigated IgE-responses in Cyp27b1-knockout (KO) mice following sensitization to OVA or intestinal infection with Heligmosomoides polygyrus Specific Igs and plasmablasts were determined by ELISA and ELISpot, Cyp27b1 expression was measured by quantitative PCR...
November 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29105119/lymphoproliferative-disorders-with-concurrent-hhv8-and-ebv-infection-beyond-primary-effusion-lymphoma-and-germinotropic-lymphoproliferative-disorder
#4
Wei Wang, Rashmi Kanagal-Shamanna, Jeffrey L Medeiros
AIMS: Lymphoproliferative disorders (LPD) characterized by human herpesvirus 8 (HHV8) and Epstein-Barr virus (EBV) infection are rare and two entities are included in the World and Health Organization classification: primary effusion lymphoma (PEL) and germinotropic LPD. These two entities have very different clinicopathological presentations and prognosis. Here we describe two cases of HHV8-positive, EBV-positive lymphoma with clinicopathological features that are not consistent with either PEL or germinotropic LPD...
November 3, 2017: Histopathology
https://www.readbyqxmd.com/read/29090101/plasmablastic-lymphoma-case-report-of-prolonged-survival-of-an-advanced-human-immunodeficiency-patient-and-literature-review
#5
Hind Rafei, Ehab El-Bahesh, Antoine Finianos, Min-Ling L Liu, Geraldine P Schechter
Clinical Practice Points. Plasmablastic lymphoma (PBL) is a rare and highly aggressive variant of diffuse large B cell lymphoma with median survival of advanced stage patients varying between 6 and 15 months in previous reports. We report here a human immunodeficiency virus-infected patient surviving over 12 years following treatment for advanced PBL with EPOCH chemotherapy and intrathecal therapy. This case highlights the potential for improved survival in PBL with intensive chemotherapy. Further, literature review suggests promising prospects utilizing novel targeted therapies to increase the rate of prolonged responses...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/29081245/primary-cutaneous-plasmablastic-lymphoma-in-an-immunocompetent-patient-is-it-associated-with-an-indolent-course
#6
Brady E Beltran, Pilar Quiñones, Gadwyn Sanchez, Antonio Paredes, Celia Moises, Esther Cotrina, Carlos A Torres-Cabala, Roberto N Miranda, Jorge J Castillo
No abstract text is available yet for this article.
October 30, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29061244/neuromyelitis-optica
#7
REVIEW
Sarah L Patterson, Sarah E Goglin
Neuromyelitis optica (NMO), formerly known as Devic disease, is an autoimmune astrocytopathic disease characterized by transverse myelitis and optic neuritis. Most patients demonstrate a relapsing course with incomplete recovery between attacks, resulting in progressive disability. The pathogenesis involves production of aquaporin-4 antibodies (AQP4-IgG) by plasmablasts in peripheral circulation, disruption of the blood-brain barrier, complement-mediated astrocyte injury, and secondary demyelination. The diagnosis relies on characteristic clinical manifestations in the presence of serum AQP4-IgG positivity or specific neuroimaging findings, and exclusion of alternative etiologies...
November 2017: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/29054606/semaphorin-4d-from-cd15-granulocytes-via-adam10-induced-cleavage-contributes-to-antibody-production-in-bullous-pemphigoid
#8
Shengxian Shen, Yao Ke, Erle Dang, Hui Fang, Yuqian Chang, Jieyu Zhang, Zhenlai Zhu, Shuai Shao, Pei Qiao, Tongmei Zhang, Hongjiang Qiao, Gang Wang
Autoreactive B cells activation and antibody production are critical events for the development of bullous pemphigoid (BP). However, the mechanism that is involved in the modulation of B cell activation and autoantibody generation has not been fully understood. Semaphorin 4D (Sema4D/CD100) plays important roles in immune regulation related to B cell, but its implication in BP remains obscure. The aim of our study was to characterize Sema4D and the underlying mechanism contributing to the autoimmune features of BP...
October 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29050819/relb-regulates-th17-differentiation-in-a-cell-intrinsic-manner
#9
Ievgen O Koliesnik, Nico Andreas, Vasily S Romanov, Sravya Sreekantapuram, Branislav Krljanac, Ronny Haenold, Falk Weih
The role of the alternative NF-κB pathway is mainly attributed to the lymphoid organ formation and blood cancer. However, its involvement in lymphocyte differentiation is not clearly defined. Recently, we have shown that uncontrolled activation of alternative NF-κB in mice lacking the NF-κB inhibitory protein p100 (p100(-/-) mice) hinders plasmablast proliferation and diminishes T cell independent responses. Here we show that hyperactivation of this pathway leads to a cell-intrinsic T cell defects. p100-deficient T helper cells displayed both an activation and a proliferation defect in vitro...
October 16, 2017: Immunobiology
https://www.readbyqxmd.com/read/29046884/selective-intrathecal-enrichment-of-g1m1-positive-b-cells-in-multiple-sclerosis
#10
Andreas Lossius, Alina Tomescu-Baciu, Trygve Holmøy, Christian A Vedeler, Egil Røsjø, Åslaug R Lorentzen, Ilaria Casetta, Frode Vartdal
Immunoglobulin gamma (IgG) heavy chain genes are associated with susceptibility to multiple sclerosis (MS) and IgG levels in the cerebrospinal fluid (CSF). However, how these variants are implicated in disease mechanisms remains unknown. Here, we show that proliferating plasmablasts expressing the G1m1 allotype of IgG1 are selectively enriched in CSF of G1m1/G1m3 heterozygous MS patients, whereas plasmablasts expressing either G1m1 or G1m3 are evenly distributed in blood. Moreover, there was a preferential intrathecal synthesis of oligoclonal IgG1 of the G1m1 allotype in heterozygous patients, whereas controls with Lyme neuroborreliosis displayed oligoclonal IgG1 of both allotypes...
October 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29033912/the-infectious-basis-of-acpa-positive-rheumatoid-arthritis
#11
REVIEW
Lazaros I Sakkas, Dimitrios Daoussis, Stamatis-Nick Liossis, Dimitrios P Bogdanos
Rheumatoid arthritis (RA) is associated with HLA-DRB1 shared epitope (HLA-DRB1SE) and anti-citrullinated protein autoantibodies (ACPAs). ACPAs precedes the onset of clinical and subclinical RA. There are strong data for three infectious agents as autoimmunity triggers in RA, namely Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans causes of periodontal disease (PD), and Epstein-Barr virus (EBV). P. gingivalis expresses arginine gingipains, that cleave proteins at the arginine residues, and peptidyl arginine deiminase (PPAD), which citrullinates arginine residues of proteins, thus forming neoantigens that lead to ACPA production...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29031828/non-progressing-cancer-patients-have-persistent-b-cell-responses-expressing-shared-antibody-paratopes-that-target-public-tumor-antigens
#12
Jeff DeFalco, Michael Harbell, Amy Manning-Bog, Gilson Baia, Alexander Scholz, Beatriz Millare, May Sumi, Danhui Zhang, Felix Chu, Christine Dowd, Patricia Zuno-Mitchell, Dongkyoon Kim, Yvonne Leung, Shuwei Jiang, Xiaobin Tang, Kevin S Williamson, Xiaomu Chen, Sean M Carroll, Gregg Espiritu Santo, Nicole Haaser, Ngan Nguyen, Eldar Giladi, David Minor, Yann Chong Tan, Jeremy B Sokolove, Lawrence Steinman, Tito A Serafini, Guy Cavet, Norman M Greenberg, Jacob Glanville, Wayne Volkmuth, Daniel E Emerling, William H Robinson
There is significant debate regarding whether B cells and their antibodies contribute to effective anti-cancer immune responses. Here we show that patients with metastatic but non-progressing melanoma, lung adenocarcinoma, or renal cell carcinoma exhibited increased levels of blood plasmablasts. We used a cell-barcoding technology to sequence their plasmablast antibody repertoires, revealing clonal families of affinity matured B cells that exhibit progressive class switching and persistence over time. Anti-CTLA4 and other treatments were associated with further increases in somatic hypermutation and clonal family size...
October 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29020226/innate-t-and-b-cell-responses-in-acute-human-zika-patients
#13
Lilin Lai, Nadine Rouphael, Yongxian Xu, Muktha S Natrajan, Allison Beck, Mari Hart, Matthew Feldhammer, Amanda Feldpausch, Charles Hill, Henry Wu, Jessica K Fairley, Pamela Lankford-Turner, Nicole Kasher, Patrick Rago, Yi-Juan Hu, Srilatha Edupuganti, Shital M Patel, Kristy O Murray, Mark J Mulligan
Background: There is an urgent need for studies of viral persistence and immunity during human Zika infections to inform planning and conduct of vaccine clinical trials. Methods: In five returned US travelers with acute symptomatic Zika infection, clinical features, viral RNA levels, and immune responses were characterized. Results: Two pregnant, flavivirus-experienced patients had viral RNA persist in plasma for >44 and >26 days. Three days after symptom onset transient increases in pro-inflammatory monocytes began followed at five days by transient decreases in myeloid dendritic cells...
August 17, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29019447/survival-of-patients-with-cd20-negative-variants-of-large-b-cell-lymphoma-an-analysis-of-the-national-cancer-data-base
#14
Lindor Qunaj, Jorge J Castillo, Adam J Olszewski
Using records from the National Cancer Data Base, we studied overall survival of CD20-negative variants of diffuse large B-cell lymphoma (DLBCL): primary effusion (PEL, N = 228), plasmablastic (PBL, N = 481), ALK-positive large B-cell (ALK + LBLC, N = 15), and human herpesvirus-8-positive DLBCL (HHV8 + DLBCL, N = 77). Three-year survival was 27% for PEL, 40% for PBL, 34% for ALK + LBCL, and 63% for HHV8 + DLBCL. Compared with unspecified DLBCL, and adjusting for clinical characteristics (including the HIV status), survival was significantly worse for PEL (hazard ratio [HR], 1...
October 11, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28993364/durable-complete-remission-with-combination-chemotherapy-and-bortezomib-in-hiv-associated-plasmablastic-lymphoma
#15
Nivedita Arora, Arjun Gupta, Navid Sadeghi
Plasmablastic lymphoma (PBL) is an aggressive form of non-Hodgkin's lymphoma (NHL) classically seen in patients infected with the human immunodeficiency virus, but can also be seen in other immunocompromised states such as transplant recipients, autoimmune diseases and the elderly. PBL is generally associated with a poor prognosis despite chemotherapy. There is evidence supporting the use of bortezomib in combination with standard chemotherapy to achieve durable responses in patients with PBL. We describe a patient with acquired immunodeficiency syndrome who presented with rectal pain and bright red blood per rectum...
October 9, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28982264/de-novo-unclassifiable-cd20-negative-diffuse-large-b-cell-lymphoma-a-diagnostic-and-therapeutic-challenge
#16
Badr AbdullGaffar, Rania M Seliem
CD20-negative diffuse large B-cell lymphomas (DLBCLs) constitute a rare and heterogeneous group of aggressive lymphomas. Known well-documented variants include plasmablastic lymphomas, primary effusion lymphomas, anaplastic kinase-positive large B-cell lymphomas, and large B-cell lymphomas arising in human herpesvirus 8 (HHV8)-associated multicentric Castleman disease. They impose diagnostic challenges for pathologists and therapeutic confrontations for clinicians. CD20 loss in B-cell lymphomas is a well-known phenomenon after rituximab therapy...
October 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28981894/principles-for-the-regulation-of-multiple-developmental-pathways-by-a-versatile-transcriptional-factor-blimp1
#17
Tadahiro Mitani, Yukihiro Yabuta, Hiroshi Ohta, Tomonori Nakamura, Chika Yamashiro, Takuya Yamamoto, Mitinori Saitou, Kazuki Kurimoto
Single transcription factors (TFs) regulate multiple developmental pathways, but the underlying mechanisms remain unclear. Here, we quantitatively characterized the genome-wide occupancy profiles of BLIMP1, a key transcriptional regulator for diverse developmental processes, during the development of three germ-layer derivatives (photoreceptor precursors, embryonic intestinal epithelium and plasmablasts) and the germ cell lineage (primordial germ cells). We identified BLIMP1-binding sites shared among multiple developmental processes, and such sites were highly occupied by BLIMP1 with a stringent recognition motif and were located predominantly in promoter proximities...
September 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28978754/neutralizing-human-monoclonal-antibodies-prevent-zika-virus-infection-in-macaques
#18
Diogo M Magnani, Thomas F Rogers, Nathan Beutler, Michael J Ricciardi, Varian K Bailey, Lucas Gonzalez-Nieto, Bryan Briney, Devin Sok, Khoa Le, Alexander Strubel, Martin J Gutman, Núria Pedreño-Lopez, Nathan D Grubaugh, Cassia G T Silveira, Helen S Maxwell, Aline Domingues, Mauricio A Martins, David E Lee, Erica E Okwuazi, Sherrie Jean, Elizabeth A Strobert, Ann Chahroudi, Guido Silvestri, Thomas H Vanderford, Esper G Kallas, Ronald C Desrosiers, Myrna C Bonaldo, Stephen S Whitehead, Dennis R Burton, David I Watkins
Therapies to prevent maternal Zika virus (ZIKV) infection and its subsequent fetal developmental complications are urgently required. We isolated three potent ZIKV-neutralizing monoclonal antibodies (nmAbs) from the plasmablasts of a ZIKV-infected patient-SMZAb1, SMZAb2, and SMZAb5-directed against two different domains of the virus. We engineered these nmAbs with Fc LALA mutations that abrogate Fcγ receptor binding, thus eliminating potential therapy-mediated antibody-dependent enhancement. We administered a cocktail of these three nmAbs to nonhuman primates 1 day before challenge with ZIKV and demonstrated that the nmAbs completely prevented viremia in serum after challenge...
October 4, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28977663/quantitative-measurement-of-18f-fdg-pet-ct-uptake-reflects-the-expansion-of-circulating-plasmablasts-in-igg4-related-disease
#19
Alvise Berti, Emanuel Della-Torre, Francesca Gallivanone, Carla Canevari, Raffaella Milani, Marco Lanzillotta, Corrado Campochiaro, Giuseppe Alvise Ramirez, Emanuele Bozzalla Cassione, Enrica Bozzolo, Federica Pedica, Isabella Castiglioni, Paolo Giorgio Arcidiacono, Gianpaolo Balzano, Massimo Falconi, Luigi Gianolli, Lorenzo Dagna
Objective: [ 18 F]Fluorodeoxyglucose ( 18 F-FDG) PET/CT is increasingly used to assess organ involvement and response to treatment in IgG4-related disease (IgG4-RD), but clear correlations between 18 F-FDG uptake and disease activity have not been established yet. We aimed to correlate the intensity and distribution of 18 F-FDG uptake with validated clinical, serological and immunological parameters of IgG4-RD activity. Methods: Twenty patients with active IgG4-RD underwent a baseline 18 F-FDG PET/CT...
July 7, 2017: Rheumatology
https://www.readbyqxmd.com/read/28970483/epitope-associated-and-specificity-focused-features-of-ev71-neutralizing-antibody-repertoires-from-plasmablasts-of-infected-children
#20
Kuan-Ying Arthur Huang, Mei-Feng Chen, Yhu-Chering Huang, Shin-Ru Shih, Cheng-Hsun Chiu, Jainn-Jim Lin, Jen-Ren Wang, Kuo-Chien Tsao, Tzou-Yien Lin
Protective antibody levels are critical for protection from severe enterovirus 71 infection. However, little is known about the specificities and functional properties of the enterovirus 71-specific antibodies induced by natural infection in humans. Here we characterize 191 plasmablast-derived monoclonal antibodies from three enterovirus 71-infected children, each of whom shows a distinct serological response. Of the 84 enterovirus 71-specific antibodies, neutralizing antibodies that target the rims and floor of the capsid canyon exhibit broad and potent activities at the nanogram level against viruses isolated in 1998-2016...
October 2, 2017: Nature Communications
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