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https://www.readbyqxmd.com/read/29127283/environmental-sensing-by-mature-b-cells-is-controlled-by-the-transcription-factors-pu-1-and-spib
#1
Simon N Willis, Julie Tellier, Yang Liao, Stephanie Trezise, Amanda Light, Kristy O'Donnell, Lee Ann Garrett-Sinha, Wei Shi, David M Tarlinton, Stephen L Nutt
Humoral immunity requires B cells to respond to multiple stimuli, including antigen, membrane and soluble ligands, and microbial products. Ets family transcription factors regulate many aspects of haematopoiesis, although their functions in humoral immunity are difficult to decipher as a result of redundancy between the family members. Here we show that mice lacking both PU.1 and SpiB in mature B cells do not generate germinal centers and high-affinity antibody after protein immunization. PU.1 and SpiB double-deficient B cells have a survival defect after engagement of CD40 or Toll-like receptors (TLR), despite paradoxically enhanced plasma cell differentiation...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29122993/the-microenvironmental-stromal-cells-abrogate-nf-%C3%AE%C2%BAb-inhibitor-induced-apoptosis-in-chronic-lymphocytic-leukemia
#2
Carl Philipp Simon-Gabriel, Katharina Foerster, Shifa Saleem, Dorothee Bleckmann, Marco Benkisser-Petersen, Nicolas Thornton, Kazuo Umezawa, Sarah Decker, Meike Burger, Hendrik Veelken, Rainer Claus, Christine Dierks, Justus Duyster, Katja Zirlik
NF-κB is known to play an important role in the pathogenesis of chronic lymphocytic leukemia. Several NF-κB inhibitors have been shown to successfully induce apoptosis of chronic lymphocytic leukemia cells in vitro. Since the microenvironment is known to be crucial for the survival of chronic lymphocytic leukemia cells, we tested here whether NF-κB inhibition may still induce apoptosis in these leukemic cells in the presence of protective stromal interaction. We used the specific NF-κB inhibitor Dehydroxymethylepoxyquinomicin...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29107213/current-and-future-treatment-options-for-pemphigus-is-it-time-to-move-towards-more-effective-treatments
#3
REVIEW
Soheil Tavakolpour
Systemic administration of corticosteroid (CS) remains the standard gold treatment for pemphigus. However, because of several long-term adverse effects, steroid-sparing agents are usually prescribed in combination with CSs. Despite the high number of available studies, the choice of best drugs to treat pemphigus remains controversial. Therapeutic approaches for pemphigus can be divided into traditional treatment and emerging ones. Personalized medicine, which aims to increase the efficacy as well as reduce adverse effects of treatments, could be considered as the future option...
December 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29100594/tumor-necrosis-factor-superfamily-member-tnfsf-13-april-and-tnfsf13b-baff-downregulate-homeostatic-immunoglobulin-production-in-the-intestines
#4
Masaaki Hashiguchi, Yuji Kashiwakura, Yumiko Kanno, Hidefumi Kojima, Tetsuji Kobata
Intestinal immunoglobulins (Igs) protect against microbes. However, the regulation of intestinal Ig production is poorly understood. In this study, we have investigated the roles of APRIL (tumor necrosis factor superfamily member [TNFSF] 13) and BAFF (TNFSF13B) in intestinal Ig induction. Peyer's patches (PPs) are, at least in part, an inductive site for Igs, including IgA. Introducing APRIL and BAFF in vivo lowered the frequency of IgG1(+) or IgG2b(+) B cells in PPs. Administration of TACI-Fc upregulated the frequency of IgG1(+), IgG2b(+), and IgA(+) B cells in PPs, suggesting that APRIL and BAFF attenuate Ig production in these regions...
October 27, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29095438/baff-is-involved-in-macrophage-induced-bortezomib-resistance-in-myeloma
#5
Jing Chen, Donghua He, Qingxiao Chen, Xing Guo, Li Yang, Xuanru Lin, Yi Li, Wenjun Wu, Yang Yang, Jingsong He, Enfan Zhang, Qing Yi, Zhen Cai
We aimed to characterize the role of B-cell activating factor (BAFF) in macrophage-mediated resistance of multiple myeloma (MM) cells to bortezomib (bort), and to further understand the molecular mechanisms involved in the process. First, we detected BAFF and its three receptors on myeloma cells and macrophages using the quantitative reverse transcriptase-polymerase chain reaction and flow cytometry. The secretion of BAFF was tested in patients with MM, MM cell lines, and macrophages. The ability of macrophages to protect MM cells from bort-induced apoptosis was significantly attenuated using BAFF-neutralizing antibody in the co-culture system or knocking down the expression of BAFF in macrophages with small interfering RNA...
November 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29079163/fingolimod-induces-baff-and-expands-circulating-transitional-b-cells-without-activating-memory-b-cells-and-plasma-cells-in-multiple-sclerosis
#6
Yusei Miyazaki, Masaaki Niino, Eri Takahashi, Masako Suzuki, Masanori Mizuno, Shin Hisahara, Toshiyuki Fukazawa, Itaru Amino, Fumihito Nakano, Masakazu Nakamura, Sachiko Akimoto, Naoya Minami, Naoto Fujiki, Shizuki Doi, Shun Shimohama, Yasuo Terayama, Seiji Kikuchi
Patients with multiple sclerosis (MS) who are treated with fingolimod have an increased proportion of transitional B cells in the circulation, but the underlying mechanism is not known. We hypothesized that B cell-activating factor of the tumor necrosis factor family (BAFF) is involved in the process. Compared with healthy controls and untreated MS patients, fingolimod-treated MS patients had significantly higher serum concentrations of BAFF, which positively correlated with the proportions and the absolute numbers of transitional B cells in blood...
October 25, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29055002/transient-baff-blockade-inhibits-type-1-diabetes-development-in-nonobese-diabetic-mice-by-enriching-immunoregulatory-b-lymphocytes-sensitive-to-deletion-by-anti-cd20-cotherapy
#7
Qiming Wang, Jeremy J Racine, Jeremy J Ratiu, Shu Wang, Rachel Ettinger, Clive Wasserfall, Mark A Atkinson, David V Serreze
In NOD mice and also likely humans, B lymphocytes play an important role as APC-expanding autoreactive T cell responses ultimately causing type 1 diabetes (T1D). Currently, humans at high future T1D risk can only be identified at late prodromal stages of disease indicated by markers such as insulin autoantibodies. When commenced in already insulin autoantibody(+) NOD mice, continuous BAFFR-Fc treatment alone or in combination with anti-CD20 (designated combo therapy) inhibited T1D development. Despite eliciting broader B lymphocyte depletion, continuous combo therapy afforded no greater T1D protection than did BAFFR-Fc alone...
October 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28992184/immune-complexes-containing-serum-b-cell-activating-factor-and-immunoglobulin-g-correlate-with-disease-activity-in-systemic-lupus-erythematosus
#8
Justa Friebus-Kardash, Leonore Branco, Camillo Ribi, Carlo Chizzolini, Uyen Huynh-Do, Denise Dubler, Pascale Roux-Lombard, Sebastian Dolff, Andreas Kribben, Ute Eisenberger, Marten Trendelenburg
Background: B-cell activating factor belonging to the TNF family (BAFF) is important for the survival of autoreactive B-cells in systemic lupus erythematosus (SLE). However, the association between serum BAFF levels and SLE disease activity is controversial. Independently, autoantibodies targeting BAFF [immunoglobulin G (IgG) anti-BAFF] have also been described in SLE patients and were associated with increased disease activity. The aim of our study was to analyse the relationship between SLE disease manifestations and serum levels of BAFF, IgG anti-BAFF and BAFF-IgG complexes...
August 8, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28989090/different-igm-b-cell-subpopulations-residing-within-the-peritoneal-cavity-of-vaccinated-rainbow-trout-are-differently-regulated-by-baff
#9
Aitor G Granja, Carolina Tafalla
In teleost fish, IgM(+) B cells are one of the main responders against inflammatory stimuli in the peritoneal cavity, as IgM(+) B cells dominate the peritoneum after intraperitoneal stimulation, also increasing the levels of secreted IgM. BAFF, a cytokine known to play a major role in B cell biology, has been shown to be up-regulated along with its receptors in the peritoneum of rainbow trout upon antigenic exposure, however, the regulatory mechanisms underneath this response remain unclear. In this study, we have identified two different IgM(+) B cell types residing in the peritoneal cavity of previously vaccinated rainbow trout (Oncorhynchus mykiss): IgD(+)IgM(hi)MHCII(hi) cells, resembling naïve B cells, and IgD(-)IgM(lo)MHCII(lo) cells, resembling antibody-secreting cells...
October 5, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28947093/decreased-tnf-family-receptor-expression-on-b-cells-is-associated-with-reduced-humoral-responses-to-streptococcus-pneumoniae-infections-in-young-children
#10
Saleem Basha, Michael E Pichichero
An underdeveloped or impaired immune response in young children is associated with increased susceptibility to Streptococcus pneumonia (Spn) infections. We determined serum antibody titers against 3 Spn vaccine candidate proteins and vaccine serotype polysaccharide antigens in a group of Spn infection prone 9-18months old and found lower IgG antibody titers to all tested antigens compared to age-matched non-infection-prone children. We also found the children had significantly reduced percentages of total memory B-cells, switched memory B-cells and plasma cells...
October 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28943879/plasma-cxcl13-but-not-b-cell-frequencies-in-acute-hiv-infection-predicts-emergence-of-cross-neutralizing-antibodies
#11
Jenniffer M Mabuka, Anne-Sophie Dugast, Daniel M Muema, Tarylee Reddy, Yathisha Ramlakhan, Zelda Euler, Nasreen Ismail, Amber Moodley, Krista L Dong, Lynn Morris, Bruce D Walker, Galit Alter, Thumbi Ndung'u
Immunological events in acute HIV-1 infection before peak viremia (hyperacute phase) may contribute to the development of broadly cross-neutralizing antibodies. Here, we used pre-infection and acute-infection peripheral blood mononuclear cells and plasma samples from 22 women, including 10 who initiated antiretroviral treatment in Fiebig stages I-V of acute infection to study B cell subsets and B-cell associated cytokines (BAFF and CXCL13) kinetics for up to ~90 days post detection of plasma viremia. Frequencies of B cell subsets were defined by flow cytometry while plasma cytokine levels were measured by ELISA...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28940789/personalized-peptide-vaccination-as-second-line-treatment-for-metastatic-upper-tract-urothelial-carcinoma
#12
Shigetaka Suekane, Kousuke Ueda, Kiyoaki Nishihara, Tetsuro Sasada, Takuto Yamashita, Noriko Koga, Shigeru Yutani, Shigeki Shichijo, Kyogo Itoh, Tsukasa Igawa, Masanori Noguchi
This study investigated the applicability of personalized peptide vaccination (PPV) for patients with metastatic upper tract urothelial cancer (mUTUC) after failure of platinum-based chemotherapy. In this single arm, open-label, phase II clinical trial, patients with mUTUC received PPV at a single institution. Personalized peptide vaccination treatment used a maximum of four peptides chosen from 27 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for six s.c. injections weekly as one cycle...
September 22, 2017: Cancer Science
https://www.readbyqxmd.com/read/28939410/human-cd40l-expressing-type-3-innate-lymphoid-cells-induce-il-10-producing-immature-transitional-regulatory-b-cells
#13
Zsolt István Komlósi, Nóra Kovács, Willem van de Veen, Anna Kirsch, Heinz Benedikt Fahrner, Marcin Wawrzyniak, Ana Rebane, Barbara Stanic, Oscar Palomares, Beate Rückert, Günter Menz, Mübeccel Akdis, György Losonczy, Cezmi A Akdis
BACKGROUND: Type 3 innate lymphoid cells (ILC3s) are involved in the maintenance of mucosal homeostasis; however, their role in immunoregulation has been unknown. Immature transitional regulatory B (itBreg) cells are innate-like B cells with immunosuppressive properties, and the in vivo mechanisms by which they are induced have not been fully clarified. OBJECTIVE: We aimed to investigate the ILC3-B cell interaction that probably takes place in human tonsils. METHODS: ILC3s were isolated from peripheral blood and palatine tonsils, expanded and cocultured with naïve B cells...
September 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28928810/characteristics-of-baff-and-april-factor-expression-in-multiple-myeloma-and-clinical-significance
#14
Jing Pan, Yuanyuan Sun, Ning Zhang, Jianming Li, Fangxin Ta, Wei Wei, Shanshan Yu, Limei Ai
The characteristics of the proliferation of B-cell activating factor (BAFF) and the proliferation-inducing ligand (APRIL) mRNA expression in mononuclear cell in multiple myeloma patients were detected, and the correlation was analyzed between the BAFF and APRIL concentrations in plasma and tumor burden parameters of multiple myeloma. Bone marrow samples from 60 patients with multiple myeloma and 20 healthy persons taken as controls, were collected. Bone marrow mononuclear cells (BMMCs) were harvested, and plasma was extracted...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28923901/maternal-serum-b-cell-activating-factor-levels-candidate-early-biomarker-for-hypertensive-disorders-of-pregnancy
#15
Hindi E Stohl, Richard H Lee, Joseph Manetta, Kristine Kikly, Lisa M Korst, William Stohl
Hypertensive disorders of pregnancy are a leading cause of maternal and perinatal morbidity and mortality. Early suppression of B-cell lymphopoiesis is necessary for a normal pregnancy. Dysregulation of factors critical to B-cell survival may result in pregnancy complications, including hypertension. In this prospective observational study at a single medical center, serum levels of BAFF (B-cell activating factor) were measured in pregnant participants at each trimester, at delivery, and postpartum and in nonpregnant controls at a single time point...
November 2017: Hypertension
https://www.readbyqxmd.com/read/28923900/diagnosing-and-treating-hypertensive-disorders-of-pregnancy-the-answer-may-now-be-less-baff-ling
#16
EDITORIAL
Christopher T Chan, Maggie Lieu, Christopher G Sobey, Grant R Drummond, Antony Vinh
No abstract text is available yet for this article.
September 18, 2017: Hypertension
https://www.readbyqxmd.com/read/28921509/baff-augments-iga2-and-il-10-production-by-tlr7-8-stimulated-total-peripheral-blood-b%C3%A2-cells
#17
Gerco den Hartog, Thijs L J van Osch, Martijn Vos, Ben Meijer, Huub F J Savelkoul, R J Joost van Neerven, Sylvia Brugman
Class-switching of B cells to IgA can be induced via both T-cell-dependent and T-cell-independent mechanisms. IgA is most predominantly produced mucosally and is important for combating infections and allergies. In contrast to mice, humans have two forms of IgA; IgA1 and IgA2 with diverse tissue distribution. In early life, IgA levels might be sub-optimal especially during the fall season when bacterial and viral infections are more common. Therefore, we investigated using human B cells whether T-cell-independent factors -promoting cell survival, class switching and immunoglobulin secretion- BAFF, APRIL, IL-10 and retinoic acid can boost IgA production in the context of viral or bacterial infection...
September 17, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28918255/microglia-mediated-baff-baffr-ligation-promotes-neuronal-survival-in-brain-ischemia-injury
#18
Kai Li, Wei Yu, Rangjuan Cao, Zhihua Zhu, Guoqing Zhao
The innate immune responses of brain to vascular occlusion are primarily orchestrated by activated microglia. However, the roles of microglia in inflammatory responses to brain ischemic injuries are controversial. Here, we report a new mechanism by which microglia confer protective effects on ischemic neuronal cells. We found that under ischemic condition, the B-cell-activating factor (BAFF) was vastly upregulated in microglia and this upregulation could at least be attributed to JAK-STAT signaling pathway activated by IFN-γ and IL-10, which were spatio-temporally enriched in I/R-injured brain as well...
November 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28916716/deregulation-of-microrna-expression-in-purified-t-and-b-lymphocytes-from-patients-with-primary-sj%C3%A3-gren-s-syndrome
#19
Shu-Fang Wang-Renault, Saida Boudaoud, Gaétane Nocturne, Elodie Roche, Nelly Sigrist, Christian Daviaud, Andreas Bugge Tinggaard, Victor Renault, Jean-François Deleuze, Xavier Mariette, Jörg Tost
OBJECTIVE: MicroRNAs (miRNAs) play an important role in the pathogenesis of autoimmune diseases such as primary Sjögren's syndrome (pSS). This study is the first to investigate miRNA expression patterns in purified T and B lymphocytes from patients with pSS using a high-throughput quantitative PCR (qPCR) approach. METHODS: Two independent cohorts of both patients with pSS and controls, one for discovery and one for replication, were included in this study. CD4+ T cells and CD19+ B cells were isolated from peripheral blood mononuclear cells by magnetic microbeads and expression of miRNAs was profiled using the Exiqon Human miRNome panel I analysing 372 miRNAs...
September 15, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28886017/b-cell-phenotype-and-igd-cd27-memory-b-cells-are-affected-by-tnf-inhibitors-and-tocilizumab-treatment-in-rheumatoid-arthritis
#20
Rita A Moura, Cláudia Quaresma, Ana R Vieira, Maria J Gonçalves, Joaquim Polido-Pereira, Vasco C Romão, Nádia Martins, Helena Canhão, João E Fonseca
BACKGROUND: The use of TNF-inhibitors and/or the IL-6 receptor antagonist, tocilizumab, in rheumatoid arthritis (RA) have pleiotropic effects that also involve circulating B-cells. The main goal of this study was to assess the effect of TNF-inhibitors and tocilizumab on B-cell phenotype and gene expression in RA. METHODS: Blood samples were collected from untreated early RA (ERA) patients, established RA patients under methotrexate treatment, established RA patients before and after treatment with TNF-inhibitors and tocilizumab, and healthy donors...
2017: PloS One
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