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Germinal B-Cell

Thomas A Ollila, Adam J Olszewski
Diffuse large B cell lymphoma (DLBCL) arises from extranodal organs in about 30% of cases. Its prognosis and risk of recurrence in the central nervous system (CNS) vary according to the primary site of origin. Recent studies begin to clarify these differences using molecular classification. Testicular, breast, and uterine DLBCL (as well as possibly primary cutaneous DLBCL, leg-type) share a high prevalence of the non-germinal center B cell (non-GCB) phenotype and the MYD88/CD79B-mutated (MCD) genotype. These biologic features, which resemble primary CNS lymphoma, may underlie their stage-independent propensity for CNS involvement...
June 21, 2018: Current Treatment Options in Oncology
Ana Isabel Pinto, Jennifer Smith, Miriam R Kissack, Karen G Hogg, E Allison Green
Type 1 diabetes (T1D) results from a coordinated autoimmune attack of insulin producing beta cells in the pancreas by the innate and adaptive immune systems, beta cell death being predominantly T cell-mediated. In addition to T cells, peripheral B cells are important in T1D progression. The thymus of mice and man also contains B cells, and lately they have been linked to central tolerance of T cells. The role of thymic B cells in T1D is undefined. Here, we show there are abnormalities in the thymic B cell compartment before beta cell destruction and T1D manifestation...
2018: Frontiers in Immunology
Arihant Jain, Sweta Rajpal, Man Updesh Singh Sachdeva, Pankaj Malhotra
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma that classically presents with rapidly enlarging lymph nodes. We present a 59-year-old man with unusual clinical presentation of numb chin syndrome (NCS) as the first symptom of disease. On evaluation, he was found to have diffuse extranodal skeletal involvement in the form of lytic-sclerotic lesions and minimal lymphadenopathy. Bone marrow biopsy revealed a poorly differentiated tumour with infarction and extensive myelofibrosis...
June 21, 2018: BMJ Case Reports
Vijayakumar Velu, Geetha Mylvaganam, Chris Ibegbu, Rama Rao Amara
T follicular helper CD4 cells (Tfh) are essential for the development and maintenance of germinal center (GC) reactions, a critical process that promotes the generation of long-lived high affinity humoral immunity. It is becoming increasingly evident that GC-Tfh cells are heterogeneous in nature with some cellular characteristics associated with a Th1, Th2, and Th17 phenotype. Emerging studies suggest that GC-Tfh cells are directed to differentiate into distinct phenotypes during chronic HIV/SIV infection and these changes in GC-Tfh cells can greatly impact the B cell response and subclass of antibodies generated...
2018: Frontiers in Immunology
James D Phelan, Ryan M Young, Daniel E Webster, Sandrine Roulland, George W Wright, Monica Kasbekar, Arthur L Shaffer, Michele Ceribelli, James Q Wang, Roland Schmitz, Masao Nakagawa, Emmanuel Bachy, Da Wei Huang, Yanlong Ji, Lu Chen, Yandan Yang, Hong Zhao, Xin Yu, Weihong Xu, Maryknoll M Palisoc, Racquel R Valadez, Theresa Davies-Hill, Wyndham H Wilson, Wing C Chan, Elaine S Jaffe, Randy D Gascoyne, Elias Campo, Andreas Rosenwald, German Ott, Jan Delabie, Lisa M Rimsza, Fausto J Rodriguez, Fayez Estephan, Matthias Holdhoff, Michael J Kruhlak, Stephen M Hewitt, Craig J Thomas, Stefania Pittaluga, Thomas Oellerich, Louis M Staudt
B cell receptor (BCR) signaling has emerged as a therapeutic target in B cell lymphomas, but inhibiting this pathway in diffuse large B cell lymphoma (DLBCL) has benefited only a subset of patients1 . Gene expression profiling identified two major DLBCL subtypes, known as germinal center (GC) B cell-like (GCB) and activated B cell-like (ABC)2,3 , with inferior outcomes following immunochemotherapy in ABC. Autoantigens drive BCR-dependent activation of NF-κB in ABC DLBCL through a kinase cascade of SYK, BTK and PKCβ to promote the assembly of the CARD11-BCL10-MALT1 (CBM) adapter complex that recruits and activates IκB kinase (IKK)4-6 ...
June 20, 2018: Nature
Talal Salem Al-Qaisi, Yu-Cheng Su, Steve R Roffler
Activation induced cytidine deaminase (AID) in germinal center B cells introduces somatic DNA mutations in transcribed immunoglobulin genes to increase antibody diversity. Ectopic expression of AID coupled with selection has been successfully employed to develop proteins with desirable properties. However, this process is laborious and time consuming because many rounds of selection are typically required to isolate the target proteins. AID expression can also adversely affect cell viability due to off target mutagenesis...
June 20, 2018: Scientific Reports
Francesco Santoro, Elena Pettini, Dmitri Kazmin, Annalisa Ciabattini, Fabio Fiorino, Gregor D Gilfillan, Ida M Evenroed, Peter Andersen, Gianni Pozzi, Donata Medaglini
Transcriptomic profiling of the immune response induced by vaccine adjuvants is of critical importance for the rational design of vaccination strategies. In this study, transcriptomics was employed to profile the effect of the vaccine adjuvant used for priming on the immune response following re-exposure to the vaccine antigen alone. Mice were primed with the chimeric vaccine antigen H56 of Mycobacterium tuberculosis administered alone or with the CAF01 adjuvant and boosted with the antigen alone. mRNA sequencing was performed on blood samples collected 1, 2, and 7 days after priming and after boosting...
2018: Frontiers in Immunology
Julia Niessl, Daniel E Kaufmann
Passive administration of broadly neutralizing antibodies (bNAbs) capable of recognizing a broad range of viral strains to non-human primates has led to protection from infection with chimeric SIV/HIV virus (SHIV). This data suggests that generating protective antibody responses could be an effective strategy for an HIV vaccine. However, classic vaccine approaches have failed so far to induce such protective antibodies in HIV vaccine trials. HIV-specific bNAbs identified in natural infection show high levels of somatic hypermutations, demonstrating that they underwent extensive affinity maturation...
June 19, 2018: Viruses
Xiaojuan Gao, Jia Li, Yaqi Wang, Shuai Liu, Baohong Yue
Recent studies show that Epstein-Barr virus (EBV) positivity might be related to adverse prognosis in patients with diffuse large B-cell lymphoma (DLBCL), but the results are still inconclusive. We conducted this meta-analysis to define the clinical value of EBV infection in DLBCL. All potential articles in PubMed, Web of Science, Medline, and Embase were retrieved. Using the random-effects or fixed-effect model, pooled hazard ratios (HRs) or relative risk (RR) with 95% confidence intervals (CIs) were used to calculate the correlation between EBER and prognosis and clinical features in DLBCL...
2018: PloS One
Elizabeth F Wallin, Danika L Hill, Michelle A Linterman, Kathryn J Wood
Background: T follicular helper (Tfh) cells are key players in the production of antibody-producing B cells via the germinal center reaction. Therapeutic strategies targeting Tfh cells are important where antibody formation is implicated in disease, such as transplant rejection and autoimmune diseases. We investigated the impact of the immunosuppressive agent tacrolimus on human Tfh cell differentiation and function in transplant recipients. Methods: Paired blood and lymph node (LN) samples were obtained from 61 transplant recipients immediately prior to organ implantation...
2018: Frontiers in Immunology
Soraya Omardien, Alexander Ter Beek, Norbert Vischer, Roy Montijn, Frank Schuren, Stanley Brul
An empirical approach was taken to screen a novel synthetic compound library designed to be active against Gram-positive bacteria. We obtained five compounds that were active against spores from the model organism Bacillus subtilis and the food-borne pathogen Bacillus cereus during our population based experiments. Using single cell live imaging we were able to observe effects of the compounds on spore germination and outgrowth. Difference in sensitivity to the compounds could be observed between B. subtilis and B...
June 14, 2018: Scientific Reports
Ellen D McPhail, Matthew J Maurer, William R Macon, Andrew L Feldman, Paul J Kurtin, Rhett P Ketterling, Rakhee Vaidya, James R Cerhan, Stephen M Ansell, Luis F Porrata, Grzegorz S Nowakowski, Thomas E Witzig, Thomas M Habermann
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-/triple-hit lymphoma) has an aggressive clinical course. We investigated prognostic value of transformation from low-grade lymphoma, cytologic features (high grade versus large cell), MYC gene rearrangement partners (immunoglobulin versus nonimmunoglobulin gene), and treatment. We evaluated 100 adults with double-/triple-hit lymphoma, reviewing cytologic features; cell of origin; and rearrangements of MYC, BCL2, and BCL6 using MYC, BCL2, and BCL6 break-apart and IGH/MYC, IGL/MYC, IGK/MYC, and IGH/BCL2 dual-fusion interphase fluorescence in situ hybridization probes...
June 14, 2018: Haematologica
Steven M Johnson, Jayadev Manikkam Umakanthan, Ji Yuan, Yuri Fedoriw, R Gregory Bociek, Kathleen Kaiser-Rogers, Jennifer N Sanmann, Nathan D Montgomery
High-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements, "double hit" or "triple hit" lymphomas (DTHL), are aggressive neoplasms associated with a poor prognosis. A t(3;8)(q27;q24) rarely occurs in B-cell lymphomas that results in a unique "pseudo-double hit" BCL6-MYC fusion, indistinguishable by interphase fluorescence in situ hybridization (FISH) from more conventional DTHL with independent MYC and BCL6 translocations. Reports of t(3;8)(q27;q24) lymphomas are sparse, and to better characterize their pathologic, cytogenetic, and clinical features, 6 new cases from 2 institutions and 19 previously published cases were reviewed...
June 11, 2018: Human Pathology
Satoshi Arai, Noriyuki Iwabuchi, Sachiko Takahashi, Jin-Zhong Xiao, Fumiaki Abe, Satoshi Hachimura
Antigen-specific immunoglobulin (Ig) A plays a major role in host defense against infections in gut mucosal tissue. Follicular helper T (Tfh) cells are located in germinal centers and promote IgA production via interactions with germinal center B cells. Several studies have demonstrated that some lactic acid bacteria (LAB) strains activate the host's acquired immune system, inducing IgA secretion in the intestine. However, the precise molecular mechanisms underlying the effects of LAB on IgA production and Tfh cells are not fully resolved...
2018: PloS One
Toshiaki Kogame, Ryosuke Yamashita, Masahiro Hirata, Tatsuki R Kataoka, Hisashi Kamido, Chiyuki Ueshima, Miho Matsui, Takashi Nomura, Kenji Kabashima
Lupus erythematosus profundus (LEP) is a variant of lupus erythematosus, involving the deep dermis and subcutaneous fat. LEP is characterized by the presence of lymphoid follicles (LF) and germinal centers (GC). However, it remains unknown whether these lymphoid structures correspond to the lymphoid tissues such as cutaneous tertiary lymphoid organs (TLO). Previously, we identified dynamically orchestrated cellular elements in murine contact dermatitis that resembled lymphoid structures, which we termed inducible skin-associated lymphoid tissues (iSALT)...
June 13, 2018: Journal of Dermatology
Erxia Shen, Qin Wang, Hardis Rabe, Wenquan Liu, Harvey Cantor, Jianmei W Leavenworth
Lineage commitment and differentiation into CD4+ T cell subsets reflect an interplay between chromatin regulators and transcription factors (TF). Follicular T cell development is regulated by the Bcl6 TF, which helps determine the phenotype and follicular localization of both CD4+ follicular helper T cells (TFH ) and follicular regulatory T cells (TFR ). Here we show that Bcl6-dependent control of follicular T cells is mediated by a complex formed between Bcl6 and the Mi-2β-nucleosome-remodeling deacetylase complex (Mi-2β-NuRD)...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ya-Li Chen, Xue-Wei Mao, Jian-Xin Wang, Luo-Yu Wu, Ming-Guo Zhou, Yi-Ping Hou
Fluazinam is a dinitroaniline fungicide with broad-spectrum activities. However, the activity of fluazinam against Bipolaris maydis which is the causal agent of southern corn leaf blight is unknown yet. In this study, baseline sensitivity of B. maydis to fluazinam was determined using 92 isolates collected during 2015 and 2016 from different geographical regions in Jiangsu Province of China, and the EC50 values ranged from 0.0396 to 0.9808 μg/ml with average value of 0.3853 ± 0.2297 μg/ml, and 0...
June 2018: Pesticide Biochemistry and Physiology
Jeong Mi Yang, Ji-Young Jang, Yoon Kyung Jeon, Jin Ho Paik
BACKGROUND: Diffuse large B cell lymphoma (DLBCL) contains heterogeneous subtypes with various molecular dysregulation at the gene, protein and microRNA levels. Compared with the GCB subtype, the non-germinal center B-like (non-GCB)/activated B cell-like (ABC) subtype exhibits frequent progression despite standard immunochemotherapy. We aimed to investigate the effects of miR-197 on the progression and chemosensitivity of DLBCL with respect to the GCB and non-GCB/ABC subtypes. METHODS: To screen distinctively expressed microRNAs, microRNA expression patterns were analyzed in 10 DLBCL cases by microarray chip assays...
June 11, 2018: Journal of Translational Medicine
Marc A Weniger, Enrico Tiacci, Stefanie Schneider, Judith Arnolds, Sabrina Rüschenbaum, Janine Duppach, Marc Seifert, Claudia Döring, Martin-Leo Hansmann, Ralf Küppers
Very few B cells in germinal centers (GCs) and extrafollicular (EF) regions of lymph nodes express CD30. Their specific features and relationship to CD30-expressing Hodgkin and Reed/Sternberg (HRS) cells of Hodgkin lymphoma are unclear but highly relevant, because numerous patients with lymphoma are currently treated with an anti-CD30 immunotoxin. We performed a comprehensive analysis of human CD30+ B cells. Phenotypic and IgV gene analyses indicated that CD30+ GC B lymphocytes represent typical GC B cells, and that CD30+ EF B cells are mostly post-GC B cells...
June 11, 2018: Journal of Clinical Investigation
Ute Greczmiel, Annette Oxenius
Chronic infections with non-cytopathic viruses constitutively expose virus-specific adaptive immune cells to cognate antigen, requiring their numeric and functional adaptation. Virus-specific CD8 T cells are compromised by various means in their effector functions, collectively termed T cell exhaustion. Alike CD8 T cells, virus-specific CD4 Th1 cell responses are gradually downregulated but instead, follicular T helper (TFH ) cell differentiation and maintenance is strongly promoted during chronic infection...
2018: Frontiers in Immunology
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