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Zhang Yiwen, Gao Shilin, Chen Yingshi, Su Lishi, Luo Baohong, Liu Chao, Li Linghua, Pan Ting, Zhang Hui
Efficient antigen presentation is indispensable for cytotoxic T lymphocyte (CTL)-mediated immunotherapy. B-lymphocytes propagated with CD40L have been developed as antigen-presenting cells (APCs), but this capacity needs further optimization. Here, we aimed to expand human B-lymphocytes on a large scale while maintaining their antigen-presenting ability by using both CD40L and B-cell activating factor (BAFF). The addition of BAFF enhanced the expansion efficiency and prolonged the culture time without causing apoptosis of the expanded B-cells...
October 21, 2016: Oncotarget
Federico Alberici, Rona M Smith, Mariana Fonseca, Lisa C Willcocks, Rachel B Jones, Julia U Holle, Stefan Wieczorek, Thomas Neumann, Davide Martorana, Gina Gregorini, Renato A Sinico, Annette Bruchfeld, Iva Gunnarsson, Sophie Ohlsson, Bo Baslund, Vladimir Tesar, Zdenka Hruskova, Maria C Cid, Augusto Vaglio, Paul A Lyons, Kenneth G C Smith, David R W Jayne
In ANCA-associated vasculitis (AAVs) response to rituximab is highly variable and predictors of response are needed. Our study identifies a single nucleotide polymorphism of the regulatory region of TNFSF13B (BAFF) associated with response to rituximab in AAV.
October 22, 2016: Journal of Allergy and Clinical Immunology
Xuyi Ma, Xiaozhou He, Panpan Dong, Dong Xue, Dan Song, Haiyan Xu, Xueguang Zhang
Objective To explore the effects of miR-338-5p on the nuclear factor κB1 (NF-κB1) expression and the IgG-producing ability of B cells. Methods Dual-luciferase reporter assay was used to test the target gene of miR-338-5p. The purified CD20(+) B cells were transfected with miR-338-5p agomiR, miR-338-5p antagomiR, NF-κB1 siRNA (siNF-κB1) and their corresponding negative control reagents, and then cultured with anti-IgM antibody and/or recombinant human B cell activating factor (rhBAFF). Real-time RCR and Western boltting were applied to determine the mRNA and protein levels of NF-κB1...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Felix M Wensveen, Erik Slinger, Martijn Ha van Attekum, Robert Brink, Eric Eldering
Upon antigen encounter, the responsive B cell pool undergoes stringent selection which eliminates cells with low B cell receptor (BCR) affinity. Already before formation of the germinal center, activated B cells of low-affinity are negatively selected in a process that is molecularly not well understood. In this study, we investigated the mechanism behind pre-GC affinity-mediated B cell selection. We applied affinity mutants of HEL antigen and found that rapidly after activation B cells become highly dependent on the cytokine BAFF...
October 20, 2016: Scientific Reports
(no author information available yet)
Corrigendum to Ragheb, S et al. (2011). Multiple sclerosis: BAFF and CXCL13 in cerebrospinal fluid Multiple Sclerosis Journal 17(07) 819-829. [DOI: 10.1177/1352458511398887].
October 2016: Multiple Sclerosis: Clinical and Laboratory Research
Robert W Hoffman, Joan T Merrill, Marta M E Alarcón-Riquelme, Michelle Petri, Ernst R Dow, Eric Nantz, Laura K Nisenbaum, Krista M Schroeder, Wendy J Komocsar, Narayanan B Perumal, Matthew D Linnik, David C Airey, Yushi Liu, Guilherme V Rocha, Richard E Higgs
OBJECTIVE: Systemic lupus erythematosus (SLE) has substantial unmet medical need and its pathogenesis is incompletely understood. This study characterized baseline gene expression and pharmacodynamic (PD)-induced changes in whole blood gene expression from two phase III, 52-week (W), randomized, placebo-controlled, double-blind studies of 1,760 SLE patients treated with the B cell activating factor (BAFF)-blocking IgG4 monoclonal antibody, tabalumab. METHODS: Patient samples were obtained from ILLUMINATE-1 and -2 while control samples were from healthy donors...
October 9, 2016: Arthritis & Rheumatology
David Chiron, Céline Bellanger, Antonin Papin, Benoit Tessoulin, Christelle Dousset, Sophie Maiga, Anne Moreau, Julie Esbelin, Valérie Trichet, Selina Chen-Kiang, Philippe Moreau, Cyrille Touzeau, Steven Le Gouill, Martine Amiot, Catherine Pellat-Deceunynck
Mantle cell lymphoma (MCL) accumulates in lymphoid organs but disseminates early on in extranodal tissues. Although proliferation remains located in lymphoid organs only, suggesting a major role of the tumor ecosystem, few studies have assessed MCL microenvironment. We therefore cocultured primary circulating MCL cells from 21 patients several weeks ex vivo with stromal or lymphoid-like (CD40L) cells to determine which interactions could support their proliferation. We showed that coculture with lymphoid-like cells, but not stromal cells, induced cell-cycle progression, which was amplified by MCL-specific cytokines (IGF-1, BAFF, IL-6, IL-10)...
October 3, 2016: Blood
Frances T Hakim, Sarfraz Memon, Ping Jin, Matin M Imanguli, Huan Wang, Najibah Rehman, Xiao-Yi Yan, Jeremy Rose, Jacqueline W Mays, Susan Dhamala, Veena Kapoor, William Telford, John Dickinson, Sean Davis, David Halverson, Haley B Naik, Kristin Baird, Daniel Fowler, David Stroncek, Edward W Cowen, Steven Z Pavletic, Ronald E Gress
Although chronic graft-versus-host disease (CGVHD) is the primary nonrelapse complication of allogeneic transplantation, understanding of its pathogenesis is limited. To identify the main operant pathways across the spectrum of CGVHD, we analyzed gene expression in circulating monocytes, chosen as in situ systemic reporter cells. Microarrays identified two interrelated pathways: 1) IFN-inducible genes, and 2) innate receptors for cellular damage. Corroborating these with multiplex RNA quantitation, we found that multiple IFN-inducible genes (affecting lymphocyte trafficking, differentiation, and Ag presentation) were concurrently upregulated in CGVHD monocytes compared with normal subjects and non-CGVHD control patients...
September 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Olfat G Shaker, Amina M Alnoury, Gehan A Hegazy, Hemmat E El Haddad, Safaa Sayed, Ahmed Hamdy
BACKGROUND: Rheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition. OBJECTIVES: The aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-β1 (TGF-β1 T869 C) and lymphotoxin-α (LT-α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-α), B-Cell Activating Factor (BAFF), and osteopontin...
September 2016: Revista Brasileira de Reumatologia
Muyao Ye, Youming Peng, Chan Liu, Wenzhe Yan, Xiaofei Peng, Liyu He, Hong Liu, Fuyou Liu
Objective. To investigate the influence of in vitro vibratory stimulation of human tonsillar mononuclear cells (TMCs). Methods. Fourteen IgA nephropathy (IgAN) patients with chronic tonsillitis (CT) and 12 CT patients with no renal pathology were enrolled. Group A TMCs were collected after 24 hours of culture and used to determine baseline levels. TMCs in groups B, C, D, E, and F were exposed to vibratory stimulation (60 Hz) for 0 (as the control group), 1, 3, 5, and 10 minutes, respectively. Results. Baseline concentrations of B-cell-activation factor (BAFF) and IgA1, BAFF mRNA expression, and aberrant O-glycosylation IgA1 level were higher in the IgAN group as compared to that in the CT group, and all increased after vibratory stimulation...
2016: BioMed Research International
Stefano Alivernini, Mariola Kurowska-Stolarska, Barbara Tolusso, Roberta Benvenuto, Aziza Elmesmari, Silvia Canestri, Luca Petricca, Antonella Mangoni, Anna Laura Fedele, Clara Di Mario, Maria Rita Gigante, Elisa Gremese, Iain B McInnes, Gianfranco Ferraccioli
MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgD(-)CD27(-) memory B-cell population in ACPA(+) RA. MiR-155 is highly expressed in RA B cells from patients with synovial tissue containing ectopic germinal centres compared with diffuse synovial tissue. MiR-155 expression is associated reciprocally with lower expression of PU...
September 27, 2016: Nature Communications
Li Zhang, Na Li, Li Yang, Jing Zhang, Hua-Wei Weng, Li-Qun Zou
B-cell activating factor (BAFF) plays important roles in a variety of lymphoid malignancies. Compared with healthy adults, patients with non-Hodgkin lymphoma had higher level of serum BAFF, and it corresponded with disease severity, response for therapy and clinical outcome. Latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus (EBV) which is a known agent of nasal, extranodal NK/T cell lymphoma (ENKTCL) can switch the BAFF activating promoter leading to higher expression of BAFF in EBV-related tumor cells...
December 2016: Cytokine
Xin Yao, Chengrong Li, Jun Yang, Guobing Wang, Changgang Li, Yu Xia
OBJECTIVE: This study aims to investigate the role of T follicular helper (TFH) cells in the immunopathogenesis of pediatric immune thrombocytopenia (ITP), as well as differences in TFH expansion and its regulation between newly diagnosed ITP (nITP) and chronic pediatric ITP (cITP). METHODS: Eighty-five children with ITP and 20 age-matched healthy controls were enrolled into this study. TFH cell frequencies and TFH cell-associated regulatory factors before and after treatment were analyzed by flow cytometry, RT-PCR and ELISA...
October 2016: Blood Cells, Molecules & Diseases
Subhajit Dasgupta
Systemic lupus erythematosus (lupus) is a female predominant autoimmune disease. The auto reactive B cells and T helper cells together are known to develop self-reactive immune responses in different tissues like kidney, bone, cardiovascular and central nervous system. Progression of disease is associated with deposition of immune complex which initiates tissue damage. The therapy for lupus still includes corticosteroids to reduce allergic manifestations and inflammatory immune responses. Recent observations suggested that, mycophenolate mofetil and cyclophosphamide treatment in combination with corticosteroids have benefit in lupus therapy...
September 12, 2016: Mini Reviews in Medicinal Chemistry
Ji Won Min, Kyoung Woon Kim, Bo-Mi Kim, Kyoung Chan Doh, Min Seok Choi, Bum Soon Choi, Cheol Whee Park, Chul Woo Yang, Yong-Soo Kim, Eun-Jee Oh, Byung Ha Chung
It is well known that pre-transplant B cell activating factor (BAFF) levels are associated with the development of de novo anti-HLA antibodies and antibody mediated rejection post-transplant. However, the clinical significance of BAFF values at allograft rejection has not been determined. In this study, we investigated the clinical significance of pre-transplant BAFF level as well as post-transplant BAFF levels measured when indication biopsy was done. We checked for anti-HLA antibodies in 115 kidney transplant recipients who required allograft biopsy due to an increase in serum creatinine...
2016: PloS One
Fernando Souza-Fonseca-Guimaraes, Stephen J Blake, Amani Makkouk, Cariad Chester, Holbrook E Kohrt, Mark J Smyth
Studies of sequential anti-CD137/anti-CD20 therapy have previously shown that the efficacy of anti-CD20 was heavily reliant upon anti-CD137; however, the exact mechanism of the anti-B-cell lymphoma efficacy, and whether this correlates with enhanced adverse effects or toxicity, had not been elucidated. Here, we observed that sequential anti-CD137 administration with anti-CD20 resulted in a synergistic therapy, largely dependent upon Fc receptors (FcR), to prolong survival in an experimental B-cell lymphoma therapy model...
July 2016: Oncoimmunology
Jiunn-Diann Lin, Yuan-Hung Wang, Wen-Fang Fang, Chia-Jung Hsiao, Amarzaya Chagnaadorj, Yuh-Feng Lin, Kam-Tsun Tang, Chao-Wen Cheng
BACKGROUND: This study investigated the association of serum B-lymphocyte activating factor (BAFF) levels with autoimmune thyroid disease (AITD) in a Chinese population. MATERIALS AND METHODS: We enrolled 221 patients with AITD [170 patients with Graves' disease (GD), 51 patients with Hashimoto's thyroiditis (HT)], and 124 healthy controls. Serum BAFF levels, thyroid function and thyroid autoantibody (TAb) levels, including of thyroid-stimulating hormone receptor antibody (TSHRAb), anti-thyroid peroxidase antibody (Anti-TPO Ab), and antithyroglobulin antibody (ATA), were measured at baseline...
November 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Andrea Doria, M Eric Gershwin, Carlo Selmi
The significant decrease in mortality rates worldwide, the increased proportion of patients achieving a durable remission, and the recent approval of a new drug after several decades are encouraging advances in the tangled history of systemic lupus erythematosus (SLE). However, when data are observed more closely, the research findings on disease pathogenesis and targeted treatments have been quite misleading, as illustrated by the central role of B cells but the missed endpoints in rituximab clinical trials which are burdened by the wide variability of SLE manifestations or the ethnic determinants of disease severity...
August 31, 2016: Journal of Autoimmunity
Alexis Garcia, Juan B De Sanctis
There have been few changes over the last 50 years in the treatment of Systemic lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: non-steroidal anti-inflammatory drugs along with the immune cell modulating agent hydroxychloroquine for mild disease, and broad spectrum immunosuppressants plus anti-inflammatories such as corticosteroids, azathioprine, cyclophosphamide, or mycophenolate during flares or severe disease with organ involvement. In some patients, the response is inadequate and side effects appear from mild unpleasant up to severe toxicity...
August 31, 2016: Current Pharmaceutical Design
Jun Xu, Ruining Han, Dae Woo Kim, Ji-Hun Mo, Yongde Jin, Ki-Sang Rha, Yong Min Kim
BACKGROUND AND OBJECTIVES: Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine. The dysregulation of IL-10 is associated with an enhanced immunopathologic response to infection, as well as with an increased risk for developing numerous autoimmune diseases. In this study, we investigated IL-10 expression in chronic rhinosinusitis with nasal polyps (CRSwNP) and assessed the possible role of IL-10 in the pathogenesis of CRSwNP. MATERIALS AND METHODS: Thirty-five patients with CRSwNP, 12 patients with chronic rhinosinusitis without NP (CRSsNP) and 10 control subjects were enrolled in this study...
2016: PloS One
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