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Germinal B-Cell

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https://www.readbyqxmd.com/read/29453292/clonal-selection-drives-protective-memory-b-cell-responses-in-controlled-human-malaria-infection
#1
Rajagopal Murugan, Lisa Buchauer, Gianna Triller, Cornelia Kreschel, Giulia Costa, Gemma Pidelaserra Martí, Katharina Imkeller, Christian E Busse, Sumana Chakravarty, B Kim Lee Sim, Stephen L Hoffman, Elena A Levashina, Peter G Kremsner, Benjamin Mordmüller, Thomas Höfer, Hedda Wardemann
Affinity maturation, the clonal selection and expansion of antigen-activated B cells expressing somatically mutated antibody variants that develop during T cell-dependent germinal center reactions, is considered pivotal for efficient development of protective B cell memory responses to infection and vaccination. Repeated antigen exposure promotes affinity maturation but each time also recruits antigen-reactive naïve B cells into the response. Here, we determined the relative impact of affinity maturation versus antigen-mediated clonal selection of naïve B cells to mount potent B cell memory responses in humans after repeated exposure to a complex pathogen, the malaria parasite Plasmodium falciparum (Pf)...
February 16, 2018: Science Immunology
https://www.readbyqxmd.com/read/29452662/pathogenesis-of-follicular-lymphoma
#2
REVIEW
Tracy Lackraj, Rashmi Goswami, Robert Kridel
Follicular lymphoma (FL) is presented as a germinal centre B cell lymphoma that is characterized by an indolent clinical course, but remains - paradoxically - largely incurable to date. The last years have seen significant progress in our understanding of FL lymphomagenesis, which is a multi-step process beginning in the bone marrow with the hallmark t(14;18)(q32;q21) translocation. The pathobiology of FL is complex and combines broad somatic changes at the level of both the genome and the epigenome, the latter evidenced by highly recurrent mutations in chromatin-modifying genes such as KMT2D and CREBBP...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29449847/potential-epigenetic-regulation-in-the-germinal-center-reaction-of-lymphoid-tissues-in-hiv-siv-infection
#3
REVIEW
Xiaolei Wang, Huanbin Xu
The production of high-affinity and broadly neutralizing antibodies plays a key role in the defense against pathogens. These antibody responses require effective germinal center (GC) reaction within anatomical niches of GCs, where follicular helper T (Tfh) cells provide cognate help to B cells for T cell-dependent antibody responses. Emerging evidences indicate that GC reaction in normal state and perhaps establishment of latent Tfh cell reservoir in HIV/SIV infection are tightly regulated by epigenetic histone modifications, which are responsible for activating or silencing chromatin...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29449308/predicting-aid-off-targets-a-step-forward
#4
Claude-Agnès Reynaud, Jean-Claude Weill
In this issue of JEM, Álvarez-Prado et al. (https://doi.org/10.1084/jem.20171738) designed a DNA capture library allowing them to identify 275 genes targeted by AID in mouse germinal center B cells. Using the molecular features of these genes to feed a machine-learning algorithm, they determined that high-density RNA PolII and Spt5 binding-found in 2.3% of the genes-are the best predictors of AID specificity.
February 15, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29448960/double-negative-cd27-igd-b-cells-are-expanded-in-nsclc-and-inversely-correlate-with-affinity-matured-b-cell-populations
#5
Sara M Centuori, Cecil J Gomes, Samuel S Kim, Charles W Putnam, Brandon T Larsen, Linda L Garland, David W Mount, Jesse D Martinez
BACKGROUND: The presence of B cells in early stage non-small cell lung cancer (NSCLC) is associated with longer survival, however, the role these cells play in the generation and maintenance of anti-tumor immunity is unclear. B cells differentiate into a variety of subsets with differing characteristics and functions. To date, there is limited information on the specific B cell subsets found within NSCLC. To better understand the composition of the B cell populations found in NSCLC we have begun characterizing B cells in lung tumors and have detected a population of B cells that are CD79A + CD27 - IgD - ...
February 15, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29447335/condition-dependent-generation-of-aquaporin-4-antibodies-from-circulating-b-cells-in-neuromyelitis-optica
#6
Robert Wilson, Mateusz Makuch, Anne-Kathrin Kienzler, James Varley, Jennifer Taylor, Mark Woodhall, Jacqueline Palace, M Isabel Leite, Patrick Waters, Sarosh R Irani
Autoantibodies to aquaporin-4 (AQP4) are pathogenic in neuromyelitis optica spectrum disorder (NMOSD). However, it is not known which B cells are the major contributors to circulating AQP4 antibodies nor which conditions promote their generation. Our experiments showed CD19+CD27++CD38++ circulating ex vivo antibody-secreting cells did not produce AQP4 antibodies under several culture conditions. To question whether other cells in circulation were capable of AQP4 antibody production, B cells were differentiated into antibody-secreting cells in vitro...
February 13, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29444938/intranasal-live-influenza-vaccine-priming-elicits-localized-b-cell-responses-in-mediastinal-lymph-nodes
#7
Sinthujan Jegaskanda, Rosemarie D Mason, Sarah F Andrews, Adam K Wheatley, Ruijun Zhang, Glennys Reynoso, David Ambrozak, Celia Santos, Catherine Luke, Yumiko Matsuoka, Jason M Brenchley, Heather D Hickman, Kawsar Talaat, Sallie R Permar, Hua-Xin Liao, Jonathan W Yewdell, Richard A Koup, Mario Roederer, Adrian B McDermott, Kanta Subbarao
Pandemic live attenuated influenza vaccines (pLAIV) prime subjects for a robust neutralizing antibody response upon subsequent administration of inactivated subunit vaccine (pISV). However, a difference was not detected in H5-specific memory B cells in the peripheral blood between pLAIV-primed and unprimed subjects prior to pISV boost. To investigate the mechanism underlying pLAIV priming, we vaccinated groups of 12 African green monkeys (AGMs) with H5N1 pISV or pLAIV alone or H5N1 pLAIV followed by pISV and examined immunity systemically and in local draining lymph nodes (LN)...
February 14, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29440708/differential-role-of-fl-bid-and-t-bid-during-verotoxin-1-induced-apoptosis-in-burkitt-s-lymphoma-cells
#8
Justine Debernardi, Emilie Hollville, Marc Lipinski, Joëlle Wiels, Aude Robert
The globotriaosylceramide Gb3 is a glycosphingolipid expressed on a subpopulation of germinal center B lymphocytes which has been recognized as the B cell differentiation antigen CD77. Among tumoral cell types, Gb3/CD77 is strongly expressed in Burkitt's lymphoma (BL) cells as well as other solid tumors including breast, testicular and ovarian carcinomas. One known ligand of Gb3/CD77 is Verotoxin-1 (VT-1), a Shiga toxin produced in specific E. coli strains. Previously, we have reported that in BL cells, VT-1 induces apoptosis via a caspase-dependent and mitochondria-dependent pathway...
February 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29440671/impaired-airway-mucociliary-function-reduces-antigen-specific-iga-immune-response-to-immunization-with-a-claudin-4-targeting-nasal-vaccine-in-mice
#9
Hidehiko Suzuki, Takahiro Nagatake, Ayaka Nasu, Huangwenxian Lan, Koji Ikegami, Mitsutoshi Setou, Yoko Hamazaki, Hiroshi Kiyono, Kiyohito Yagi, Masuo Kondoh, Jun Kunisawa
Vaccine delivery is an essential element for the development of mucosal vaccine, but it remains to be investigated how physical barriers such as mucus and cilia affect vaccine delivery efficacy. Previously, we reported that C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) targeted claudin-4, which is expressed by the epithelium associated with nasopharynx-associated lymphoid tissue (NALT), and could be effective as a nasal vaccine delivery. Mice lacking tubulin tyrosine ligase-like family, member 1 (Ttll1-KO mice) showed mucus accumulation in nasal cavity due to the impaired motility of respiratory cilia...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29440639/the-small-gtpase-rhou-lays-downstream-of-jak-stat-signaling-and-mediates-cell-migration-in-multiple-myeloma
#10
Sara Canovas Nunes, Martina Manzoni, Marco Pizzi, Elisa Mandato, Marilena Carrino, Laura Quotti Tubi, Renato Zambello, Fausto Adami, Andrea Visentin, Gregorio Barilà, Livio Trentin, Sabrina Manni, Antonino Neri, Gianpietro Semenzato, Francesco Piazza
Multiple myeloma is a post-germinal center B-cell neoplasm, characterized by the proliferation of malignant bone marrow plasma cells, whose survival and proliferation is sustained by growth factors and cytokines present in the bone marrow microenvironment. Among them, IL-6 triggers the signal downstream of its receptor, leading to the activation of the JAK/STAT pathway. The atypical GTPase RhoU lays downstream of STAT3 transcription factor and could be responsible for mediating its effects on cytoskeleton dynamics...
February 13, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29426881/activated-t-follicular-helper-like-cells-are-released-into-blood-after-oral-vaccination-and-correlate-with-vaccine-specific-mucosal-b-cell-memory
#11
Ana Cárdeno, Maria K Magnusson, Marianne Quiding-Järbrink, Anna Lundgren
T follicular helper (Tfh)-like cells with potent B-cell helping ability are mobilized into human circulation after parenteral vaccination and are generally held to reflect ongoing germinal center reactions. However, whether mucosal vaccination induces systemic Tfh responses and how such responses may relate to IgA production are unknown. We investigated the frequencies, phenotype and function of circulating Tfh-like CD4+CXCR5+ T cells (cTfh) in adults receiving an oral inactivated enterotoxigenic Escherichia coli vaccine...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29423005/transcription-factor-phf19-positively-regulates-germinal-center-reactions-that-underlies-its-role-in-rheumatoid-arthritis
#12
Fanyou Ning, Chong Wang, Suling Niu, Haiyan Xu, Kai Xia, Nan Wang
The Polycomb Repressive Complex 2 (PRC2) component PHD Finger Protein 19 (phf19) gene has been identified to be associated with rheumatoid arthritis (RA) risk. Here we show that Phf19 is highly expressed in murine germinal centers (GCs) and RA patients. To investigate the function of Phf19 in lymphocytes, we generated RAG1-deficient mice reconstituted with Phf19 or control-vector transduced bone marrow (BM) cells. Lymphogenesis in primary lymphoid tissues of Phf19-RM is normal, however, Phf19-RM form enlarged GCs and generate more antibody-secreting cells (ASCs)...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29422894/the-b-cell-follicle-in-hiv-infection-barrier-to-a-cure
#13
REVIEW
Matthew P Bronnimann, Pamela J Skinner, Elizabeth Connick
The majority of HIV replication occurs in secondary lymphoid organs (SLOs) such as the spleen, lymph nodes, and gut-associated lymphoid tissue. Within SLOs, HIV RNA+ cells are concentrated in the B-cell follicle during chronic untreated infection, and emerging data suggest that they are a major source of replication in treated disease as well. The concentration of HIV RNA+ cells in the B-cell follicle is mediated by several factors. Follicular CD4+ T-cell subsets including T-follicular helper cells and T-follicular regulatory cells are significantly more permissive to HIV than extrafollicular subsets...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29420557/capillary-networks-and-follicular-marginal-zones-in-human-spleens-three-dimensional-models-based-on-immunostained-serial-sections
#14
Birte S Steiniger, Christine Ulrich, Moritz Berthold, Michael Guthe, Oleg Lobachev
We have reconstructed small parts of capillary networks in the human splenic white pulp using serial sections immunostained for CD34 alone or for CD34 and CD271. The three-dimensional (3D) models show three types of interconnected networks: a network with very few long capillaries inside the white pulp originating from central arteries, a denser network surrounding follicles plus periarterial T-cell regions and a network in the red pulp. Capillaries of the perifollicular network and the red pulp network have open ends...
2018: PloS One
https://www.readbyqxmd.com/read/29416939/maturation-of-tertiary-lymphoid-structures-and-recurrence-of-stage-ii-and-iii-colorectal-cancer
#15
Florian Posch, Karina Silina, Sebastian Leibl, Axel Mündlein, Holger Moch, Alexander Siebenhüner, Panagiotis Samaras, Jakob Riedl, Michael Stotz, Joanna Szkandera, Herbert Stöger, Martin Pichler, Roger Stupp, Maries van den Broek, Peter Schraml, Armin Gerger, Ulf Petrausch, Thomas Winder
Tertiary lymphoid structures (TLS) are associated with favorable outcome in non-metastatic colorectal carcinoma (nmCRC), but the dynamics of TLS maturation and its association with effective anti-tumor immune surveillance in nmCRC are unclear. Here, we hypothesized that not only the number of TLS but also their composition harbors information on recurrence risk in nmCRC. In a comprehensive molecular, tissue, laboratory, and clinical analysis of 109 patients with stage II/III nmCRC, we assessed TLS numbers and degree of maturation in surgical specimens by multi-parameter immunofluorescence of follicular dendritic cell (FDC) and germinal center (GC) markers...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29416540/induction-of-short-nfatc1-%C3%AE-a-isoform-interferes-with-peripheral-b-cell-differentiation
#16
Khalid Muhammad, Ronald Rudolf, Duong Anh Thuy Pham, Stefan Klein-Hessling, Katsuyoshi Takata, Nobuko Matsushita, Volker Ellenrieder, Eisaku Kondo, Edgar Serfling
In lymphocytes, immune receptor signals induce the rapid nuclear translocation of preformed cytosolic NFAT proteins. Along with co-stimulatory signals, persistent immune receptor signals lead to high levels of NFATc1/αA, a short NFATc1 isoform, in effector lymphocytes. Whereas NFATc1 is not expressed in plasma cells, in germinal centers numerous centrocytic B cells express nuclear NFATc1/αA. When overexpressed in chicken DT40 B cells or murine WEHI 231 B cells, NFATc1/αA suppressed their cell death induced by B cell receptor signals and affected the expression of genes controlling the germinal center reaction and plasma cell formation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29414660/increased-circulating-cd4-cxcr5-foxp3-follicular-regulatory-t-cells-correlated-with-severity-of-systemic-lupus-erythematosus-patients
#17
Chen Liu, Dongwei Wang, Ying Song, Songsong Lu, Jingzhong Zhao, Hui Wang
As one specialized subset of regulatory T cells (Tregs), follicular regulatory T cells (TFR) could suppress follicular helper T cells (TFH) and B cells in germinal centers to maintain immune homeostasis. The unbalance of TFR and TFH cells could result in abnormal germinal center responses and contribute to pathogenesis of autoimmune diseases. However, the role of TFR cells in systemic lupus erythematosus (SLE) remains unclear. This study revealed a significant increase of CD4+CXCR5+FOXP3+ TFR cells in peripheral blood of SLE patients compared with healthy controls...
January 30, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29412920/effects-of-uv-b-radiation-on-the-isoflavone-accumulation-and-physiological-biochemical-changes-of-soybean-during-germination-physiological-biochemical-change-of-germinated-soybean-induced-by-uv-b
#18
Meng Ma, Pei Wang, Runqiang Yang, Zhenxin Gu
In this study, the effects of UV-B radiation on the isoflavones accumulation, physiological and nutritional quality, water status, and characteristics of proteins in germinated soybeans were investigated. The results showed that isoflavones content in soybeans increased with appropriate intensity and time of UV-B radiation and decreased with excessive treatment. Fresh weight, length, free amino acids, reducing sugar contents and bulk water (T23) in germinated soybeans decreased with increasing radiation time, indicating that UV-B inhibited the growth and nutrients metabolism of soybean during germination...
June 1, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29410210/characterization-of-three-mitogen-activated-protein-kinase-kinase-like-proteins-in-beauveria-bassiana
#19
Jing Liu, Huan-Huan Sun, Sheng-Hua Ying, Ming-Guang Feng
Pbs2, Mkk1 and Ste7 orthologs are three mitogen-activated protein kinase (MAPK) kinases (MAPKKs) acting as checkpoints of the Hog1, Slt2 and Fus3 MAPK cascades that constitute major parts of fungal signaling network. Here, we show that three other MAPKK-like proteins (Mkk4/5/6) exist in Beauveria bassiana and other entomopathogenic or non-entomopathogenic fungi but lack in yeasts and aspergilli, and elucidate how they function in the fungal insect pathogen. Based on phenotypic defects of single-, double- and triple-deletion mutants, Mkk4, Mkk5 and Mkk6 played collaborative or independent roles in sustaining radial growth on various media, conidiation capacity, conidial germination, conidial UV-B resistance, and/or virulence...
February 2, 2018: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/29408330/new-human-combined-immunodeficiency-due-to-irf4-deficiency-inherited-by-uniparental-isodisomy
#20
María Bravo García-Morato, Francisco Javier Aracil Santos, Alejandro Contreras Briones, Alfonso Blázquez Moreno, Ángela Del Pozo Maté, Ángeles Domínguez-Soto, María José Beato Merino, Lucía Del Pino Molina, Juan Torres Canizales, Ana Victoria Marin, Elena Vallespín García, Marta Feito Rodríguez, Diego Plaza López Sabando, Anaïs Jiménez-Reinoso, Yasmina Mozo Del Castillo, Francisco José Sanz Santaeufemia, Raúl de Lucas-Laguna, Paula Cárdenas, Laura Casamayor Polo, María Coronel Díaz, Mar Valés-Gómez, Ernesto Roldán Santiago, Antonio Ferreira Cerdán, Julián Nevado Blanco, Ángel L Corbí, Hugh T Reyburn, José Ramón Regueiro, Eduardo López-Granados, Rebeca Rodríguez Pena
BACKGROUND: Interferon regulatory factor 4 (IRF4) is a fundamental transcription factor in adaptive and innate immunity, due to its key role in the differentiation and functional specialization of lymphoid and myeloid lineage cells. In mouse models, IRF4 participates in bone marrow central tolerance, naïve B cell activation, germinal centre formation, plasma cell differentiation, immunoglobulin secretion, T helper subset differentiation, macrophage polarization, and dendritic cell differentiation, among other processes...
February 2, 2018: Journal of Allergy and Clinical Immunology
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