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https://www.readbyqxmd.com/read/28446568/lis1-regulates-germinal-center-b-cell-antigen-acquisition-and-affinity-maturation
#1
Jingjing Chen, Zhenming Cai, Le Zhang, Yuye Yin, Xufeng Chen, Chao Chen, Yang Zhang, Sulan Zhai, Xuehui Long, Xiaolong Liu, Xiaoming Wang
The germinal center (GC) is the site where activated B cells undergo rapid expansions, somatic hypermutation, and affinity maturation. Affinity maturation is a process of Ag-driven selection. The amount of Ag acquired and displayed by GC B cells determines whether it can be positively selected, and therefore Ag acquisition has to be tightly regulated to ensure the efficient affinity maturation. Cell expansion provides sufficient quantity of GC B cells and Abs, whereas affinity maturation improves the quality of Abs...
April 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28445143/the-igh-locus-relocalizes-to-a-recombination-compartment-in-the-perinucleolar-region-of-differentiating-b-lymphocytes
#2
Andrey Pichugin, Olga V Iarovaia, Alexey Gavrilov, Ilya Sklyar, Natalja Barinova, Aleksandr Barinov, Evgeny Ivashkin, Gersende Caron, Said Aoufouchi, Sergey V Razin, Thierry Fest, Marc Lipinski, Yegor S Vassetzky
The immunoglobulin heavy chain (IGH) gene loci are subject to specific recombination events during B-cell differentiation including somatic hypermutation and class switch recombination which mark the end of immunoglobulin gene maturation in germinal centers of secondary lymph nodes. These two events rely on the activity of activation-induced cytidine deaminase (AID) which requires DNA double strand breaks be created, a potential danger to the cell. Applying 3D-fluorescence in situ hybridization coupled with immunofluorescence staining to a previously described experimental system recapitulating normal B-cell differentiation ex vivo, we have kinetically analyzed the radial positioning of the two IGH gene loci as well as their proximity with the nucleolus, heterochromatin and γH2AX foci...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443628/intestinal-microbiota-link-lymphopenia-to-murine-autoimmunity-via-pd-1-cxcr5-dim-b-helper-t-cell-induction
#3
Toshiki Eri, Kimito Kawahata, Takeyuki Kanzaki, Mitsuru Imamura, Kazuya Michishita, Lisa Akahira, Ei Bannai, Noritada Yoshikawa, Yasumasa Kimura, Takeshi Satoh, Satoshi Uematsu, Hirotoshi Tanaka, Kazuhiko Yamamoto
T cell lymphopenia results in peripheral homeostatic expansion to maintain the T cell immune system, which is termed lymphopenia-induced proliferation (LIP). LIP is a potential risk for expanding autoreactive clones to become pathogenic in human and murine autoimmune diseases. However, the ontogeny of T cells that induce autoantibody production by autoreactive B cells in LIP remains unclear. Transfer of CD4(+)CD25(-) conventional T (Tc) cells into T-cell-deficient athymic nude mice has been previously reported as a LIP-induced autoimmune model which develops organ-specific autoimmune diseases and systemic antinuclear antibodies (ANAs)...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442562/ebv-germinates-lymphoma-from-the-germinal-center-in-a-battle-with-t-and-nk-cells
#4
Kamonwan Fish, Richard Longnecker
No abstract text is available yet for this article.
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438623/ezh2-overexpression-in-primary-gastrointestinal-diffuse-large-b-cell-lymphoma-and-its-association-with-the-clinicopathological-features
#5
Yang Liu, Kangjie Yu, Mingyang Li, Kaixuan Zeng, Jie Wei, Xia Li, Yixiong Liu, Danhui Zhao, Linni Fan, Zhou Yu, Yingmei Wang, Zengshan Li, Wei Zhang, Qingxian Bai, Qingguo Yan, Ying Guo, Zhe Wang, Shuangping Guo
Gastrointestinal diffuse large B cell lymphoma (GI DLBCL) is the most common gastrointestinal lymphoma, Enhancer of zeste homolog 2 (EZH2) have been implicated in the pathogenesis of several cancers. However, EZH2 has not been studied in GI DLBCL. Thus, we investigated EZH2 expression and EZH2 Y641 mutation in 100 GI DLBCL specimens by immunohistochemistry and sequencing. In addition, trimethylated H3K27 (H3K27me3), BCL2, c-MYC, and Ki-67 expression and Helicobacter pylori infection were detected, and BCL2 and c-MYC gene translocation were assessed...
April 21, 2017: Human Pathology
https://www.readbyqxmd.com/read/28436953/disruption-of-direct-3d-telomere-trf2-interaction-through-two-molecularly-disparate-mechanisms-is-a-hallmark-of-primary-hodgkin-and-reed-sternberg-cells
#6
Hans Knecht, Nathalie A Johnson, Tina Haliotis, Daniel Lichtensztejn, Sabine Mai
In classical Hodgkin's lymphoma (cHL), specific changes in the 3D telomere organization cause progression from mononuclear Hodgkin cells (H) to multinucleated Reed-Sternberg cells (RS). In a post-germinal center B-cell in vitro model, permanent latent membrane protein 1 (LMP1) expression, as observed in Epstein-Barr virus (EBV)-associated cHL, results in multinuclearity and complex chromosomal aberrations through downregulation of key element of the shelterin complex, the telomere repeat binding factor 2 (TRF2)...
April 24, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28432871/mir-24-3p-is-overexpressed-in-hodgkin-lymphoma-and-protects-hodgkin-and-reed-sternberg-cells-from-apoptosis
#7
Ye Yuan, Joost Kluiver, Jasper Koerts, Debora de Jong, Bea Rutgers, Fazlyn Reeny Abdul Razak, Martijn Terpstra, Boudewijn Plaat, Ilja M Nolte, Arjan Diepstra, Lydia Visser, Klaas Kok, Anke van den Berg
miRNAs play important roles in biological processes, such as proliferation, metabolism, differentiation, and apoptosis, whereas altered expression levels contribute to diseases, such as cancers. We identified miRNAs with aberrant expression in Hodgkin lymphoma (HL) and investigated their role in pathogenesis. Small RNA sequencing revealed 84 significantly differentially expressed miRNAs in HL cell lines as compared to germinal center B cells. Three up-regulated miRNAs-miR-23a-3p, miR-24-3p, and miR-27a-3p-were derived from one primary miRNA transcript...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28430952/a-strategy-for-helicobacter-immunohistochemistry-utilization-in-pediatric-practice-%C3%A2-insights-from-morphologic-and-cost-benefit-analyses
#8
Miriam R Conces, Christina A Arnold, Peter B Baker, Christopher M Carter, Bonita Fung, Vinay Prasad, Michael A Arnold
Objectives: Recent studies in adults have examined the utility of immunohistochemistry (IHC) in detecting Helicobacter in gastric biopsy specimens and reached differing conclusions. Dedicated cost-benefit analysis of Helicobacter IHC in pediatric gastric biopsy specimens has not been performed. Methods: From 1,955 pediatric gastric biopsies in a 1-year period, we identified 63 Helicobacter -positive and 120 Helicobacter -negative biopsy specimens. All cases were scored according to the Updated Sydney System for the severity of inflammation...
November 1, 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28429361/pathologic-character-and-diagnosis-of-female-primary-genital-system-diffuse-large-b-cell-lymphoma
#9
H Cheng, X Tang, J Cheng, B Zhang, Y-L Zhang, W-Q Wang, P Teng
OBJECTIVE: We investigated the clinicopathological characteristics and immunophenotype of female genital system diffuse large B-cell lymphoma (DLBCL) in order to improve diagnosis and therapy efficacy. PATIENTS AND METHODS: The clinicopathologic features of 13 cases with primary DLBCL of the female genital system were studied retrospectively. According to the immunophenotypes, 10 cases were classified as germinal center B-cell-like DLBCL and the other 3 as non-center B-cell-like DLBCL...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28428103/characteristics-and-clinical-implications-of-reactive-germinal-centers-in-the-bone-marrow
#10
Rose Lou Marie C Agbay, L Jeffrey Medeiros, Joseph D Khoury, Alireza Salem, Carlos E Bueso-Ramos, Sanam Loghavi
Reactive germinal centers (GCs) in the bone marrow (BM) have been described in patients with autoimmune disorders, infections, malignancies and following certain drug therapies, or as an isolated finding without obvious underlying disease. In this study, we describe the clinical conditions in which reactive GCs occur in BM samples, and their topography and accompanying laboratory and ancillary findings in the setting of a cancer center. We identified 32 BM specimens with reactive GCs with an estimated frequency of <0...
April 17, 2017: Human Pathology
https://www.readbyqxmd.com/read/28426555/creating-artificial-lymphoid-tissues-to-study-immunity-and-hematological-malignancies
#11
Shivem B Shah, Ankur Singh
PURPOSE OF REVIEW: The specialized microenvironments of lymphoid tissue affect immune cell function and progression of disease. However, current animal models are low throughput and a large number of human diseases are difficult to model in animals. Animal models are less amenable to manipulation of tissue niche components, signalling pathways, epigenetics, and genome editing than ex vivo models. On the other hand, conventional 2D cultures lack the physiological relevance to study precise microenvironmental interactions...
April 19, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28423735/the-long-non-coding-rna-nonhsag026900-predicts-prognosis-as-a-favorable-biomarker-in-patients-with-diffuse-large-b-cell-lymphoma
#12
Shuangtao Zhao, Shuangsang Fang, Yanhua Liu, Xixi Li, Shengyou Liao, Jinwen Chen, Jingjia Liu, Lianhe Zhao, Hui Li, Wei Zhou, Wenzhi Shen, Xiaoli Dong, Rong Xiang, Luhua Wang, Yi Zhao
Long non-coding RNAs are known to be involved in cancer progression, but their biological functions and prognostic values are still largely unexplored in diffuse large B-cell lymphoma. In this study, long non-coding RNAs expression was characterized in 1,403 samples including normal and diffuse large B-cell lymphoma by repurposing 7 microarray datasets. Compared with any stage of normal B cells, NONHSAG026900 expression was significantly decreased in tumor samples. And in germinal center B-cell subtype, the significantly higher expression of NONHSAG026900 indicated it was a favorable prognosis biomarker...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423544/cell-of-origin-of-diffuse-large-b-cell-lymphomas-determined-by-the-lymph2cx-assay-better-prognostic-indicator-than-hans-algorithm
#13
Nara Yoon, Soomin Ahn, Hae Yong Yoo, Suk Jin Kim, Won Seog Kim, Young Hyeh Ko
Diffuse large B-cell lymphomas (DLBCLs) are clinically heterogeneous and need a biomarker that can predict the outcome of treatments accurately. To assess the prognostic significance of the cell-of-origin type for DLBCLs, we applied the Lymph2Cx assay using a NanoString gene expression platform on formalin-fixed paraffin wax-embedded pretreatment tissues obtained from 82 patients with de novo DLBCL, not otherwise specified. All patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as the first line of chemotherapy...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423310/c-myb-regulates-the-t-bet-dependent-differentiation-program-in-b-cells-to-coordinate-antibody-responses
#14
Dana Piovesan, Jessica Tempany, Andrea Di Pietro, Inge Baas, Callisthenis Yiannis, Kristy O'Donnell, Yunshun Chen, Victor Peperzak, Gabrielle T Belz, Charles R Mackay, Gordon K Smyth, Joanna R Groom, David M Tarlinton, Kim L Good-Jacobson
Humoral immune responses are tailored to the invading pathogen through regulation of key transcription factors and their networks. This is critical to establishing effective antibody-mediated responses, yet it is unknown how B cells integrate pathogen-induced signals to drive or suppress transcriptional programs specialized for each class of pathogen. Here, we detail the key role of the transcription factor c-Myb in regulating the T-bet-mediated anti-viral program. Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3 expression by upregulating T-bet, normally suppressed during Th2-cell-mediated responses...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28422791/intrastructural-help-improving-the-hiv-1-envelope-antibody-response-induced-by-virus-like-particle-vaccines
#15
Vladimir Temchura, Klaus Überla
PURPOSE OF REVIEW: The importance of IgG Fc-effector functions for the efficacy of HIV vaccines is increasingly recognized. Although different types of vaccines were shown to induce antibodies with different Fc-activities, there is no clear strategy how to raise antibody responses with a desired pattern of Fc-effector functions. Given the central role of T-helper cells in regulating the germinal center reaction and the differentiation of B cells in an antigen-specific manner, the review will discuss whether T-helper cells directed against non-HIV envelope (Env) antigens could be harnessed to improve the HIV-Env antibody response...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422784/b-cell-abnormalities-and-impact-on-antibody-response-in-hiv-infection
#16
Alessandra Noto, Giuseppe Pantaleo
PURPOSE OF REVIEW: The purpose of the present review is to provide an update on the current development in the field of broadly neutralizing antibodies (bNabs) and their potential use in the prevention and therapeutic settings, and an evaluation of the B-cell abnormalities that may impair antibody responses in HIV infection. RECENT FINDINGS: Major advances have been achieved in the characterization of bNabs directed against different vulnerable regions of HIV Envelope (Env)...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28416503/invariant-natural-killer-t-cells-ameliorate-murine-chronic-gvhd-by-expanding-donor-regulatory-t-cells
#17
Jing Du, Katelyn Paz, Govindarajan Thangavelu, Dominik Schneidawind, Jeanette Baker, Ryan Flynn, Omar Duramad, Colby Feser, Angela Panoskaltsis-Mortari, Robert S Negrin, Bruce R Blazar
Chronic graft-versus-host-disease (cGVHD) can cause multi-organ system disease typically with autoimmune-like features, resulting in high mortality and morbidity due to treatment limitations. Invariant natural killer T cells (iNKTs), a small population characterized by expression of a semi-invariant T-cell receptor, rapidly produce copious amounts of diverse cytokines upon activation that exert potent immune regulatory function. Here, we show that iNKTs are significantly reduced in a cGVHD murine model that recapitulates several aspects of autoimmunity and organ fibrosis observed in cGVHD patients...
April 17, 2017: Blood
https://www.readbyqxmd.com/read/28416490/preclinical-characterization-of-bet-family-bromodomain-inhibitor-abbv-075-suggests-combination-therapeutic-strategies
#18
Mai H Bui, Xiaoyu Lin, Daniel H Albert, Leiming Li, Lloyd T Lam, Emily J Faivre, Scott Warder, Xiaoli Huang, Denise Wilcox, Cherrie K Donawho, George S Sheppard, Le Wang, Steve Fidanze, John K Pratt, Dachun Liu, Lisa Hasvold, Tamar Uziel, Xin Lu, Fred Kohlhapp, Guowei Fang, Steven W Elmore, Saul H Rosenberg, Keith F McDaniel, Warren M Kati, Yu Shen
ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered Phase I clinical trials. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models representing a variety of hematological malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G1 cell cycle arrest without extensive apoptosis. In this study, we show that ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) cells...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28414328/marginal-zone-b-cells-control-the-response-of-follicular-helper-t-cells-to-a-high-cholesterol-diet
#19
Meritxell Nus, Andrew P Sage, Yuning Lu, Leanne Masters, Brian Y H Lam, Stephen Newland, Sandra Weller, Dimitrios Tsiantoulas, Juliette Raffort, Damiënne Marcus, Alison Finigan, Lauren Kitt, Nichola Figg, Reinhold Schirmbeck, Manfred Kneilling, Giles S H Yeo, Christoph J Binder, José Luis de la Pompa, Ziad Mallat
Splenic marginal zone B (MZB) cells, positioned at the interface between circulating blood and lymphoid tissue, detect and respond to blood-borne antigens. Here we show that MZB cells in mice activate a homeostatic program in response to a high-cholesterol diet (HCD) and regulate both the differentiation and accumulation of T follicular helper (TFH) cells. Feeding mice an HCD resulted in upregulated MZB cell surface expression of the immunoregulatory ligand PDL1 in an ATF3-dependent manner and increased the interaction between MZB cells and pre-TFH cells, leading to PDL1-mediated suppression of TFH cell motility, alteration of TFH cell differentiation, reduced TFH abundance and suppression of the proatherogenic TFH response...
April 17, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28408984/b-cell-tolerance-and-autoimmunity
#20
REVIEW
Takeshi Tsubata
Self-reactive B cells are tolerized at various stages of B-cell development and differentiation, including the immature B-cell stage (central tolerance) and the germinal center (GC) B-cell stage, and B-cell tolerance involves various mechanisms such as deletion, anergy, and receptor editing. Self-reactive B cells generated by random immunoglobulin variable gene rearrangements are tolerized by central tolerance and anergy in the periphery, and these processes involve apoptosis regulated by Bim, a pro-apoptotic member of the Bcl-2 family, and regulation of B-cell signaling by various phosphatases, including SHIP-1 and SHP-1...
2017: F1000Research
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