The Experts below are selected from a list of 32610 Experts worldwide ranked by ideXlab platform
Caroline Torring - One of the best experts on this subject based on the ideXlab platform.
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the B1 Cell suBpopulation is diminished in patients with relapsing remitting multiple sclerosis
Journal of Neuroimmunology, 2013Co-Authors: Caroline Torring, Charlotte Christie Petersen, Lasse Bjerg, Emil Kofodolsen, Thor Petersen, Per HöllsbergAbstract:ABstract B Cell suBsets in newly diagnosed untreated, relapsing–remitting multiple sclerosis (MS) patients were examined. The fraction of CD20+ B Cells was significantly increased in MS. Among suBsets of B Cells, MS patients had increased frequency of naive Cells, But reduced frequency of memory and B1 Cells. The frequencies of B1 Cells were inversely correlated with the time since last attack. B1 Cells resemBled the phenotype of either lymphocytes (CD11B− B1 Cells) or monocytes (CD11B+ B1 Cells) and a small fraction of Cells was CD3+CD20+ By confocal microscopy.
Amit Baror - One of the best experts on this subject based on the ideXlab platform.
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dimethyl fumarate treatment mediates an anti inflammatory shift in B Cell suBsets of patients with multiple sclerosis
Journal of Immunology, 2017Co-Authors: Ayman Rezk, Mathab Ghadiri, Felix Luessi, Frauke Zipp, Paul S Giacomini, Jack P Antel, Amit BarorAbstract:The therapeutic mode of action of dimethyl fumarate (DMF), approved for treating patients with relapsing-remitting multiple sclerosis, is not fully understood. Recently, we and others demonstrated that AB-independent functions of distinct B Cell suBsets are important in mediating multiple sclerosis (MS) relapsing disease activity. Our oBjective was to test whether and how DMF influences Both the phenotype and functional responses of disease-implicated B Cell suBsets in patients with MS. High-quality PBMC were oBtained from relapsing-remitting MS patients prior to and serially after initiation of DMF treatment. Multiparametric flow cytometry was used to monitor the phenotype and functional response-profiles of distinct B Cell suBsets. Total B Cell counts decreased following DMF treatment, largely reflecting losses of circulating mature/differentiated (But not of immature transitional) B Cells. Within the mature B Cell pool, DMF had a greater impact on memory than naive B Cells. In keeping with these in vivo effects, DMF treatment in vitro remarkaBly diminished mature (But not transitional B Cell) survival, mediated By inducing apoptotic Cell death. Although DMF treatment (Both in vivo and in vitro) minimally impacted B Cell IL-10 expression, it strongly reduced B Cell expression of GM-CSF, IL-6, and TNF-α, resulting in a significant anti-inflammatory shift of B Cell response profiles. The DMF-mediated decrease in B Cell proinflammatory cytokine responses was further associated with reduced phosphorylation of STAT5/6 and NF-κB in surviving B Cells. Together, these data implicate novel mechanisms By which DMF may modulate MS disease activity through shifting the Balance Between pro- and anti-inflammatory B Cell responses.
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distinct effector cytokine profiles of memory and naive human B Cell suBsets and implication in multiple sclerosis
Journal of Immunology, 2007Co-Authors: Martin Duddy, Masaaki Niino, Femina Adatia, Sherry Hebert, Mark S Freedman, Harry Atkins, Ho Jin Kim, Amit BarorAbstract:Although recent animal studies have fuelled growing interest in AB-independent functions of B Cells, relatively little is known aBout how human B Cells and their suBsets may contriBute to the regulation of immune responses in either health or disease. In this study, we first confirm that effector cytokine production By normal human B Cells is context dependent and demonstrate that this involves the reciprocal regulation of proinflammatory and anti-inflammatory cytokines. We further report that this cytokine network is dysregulated in patients with the autoimmune disease multiple sclerosis, whose B Cells exhiBit a decreased average production of the down-regulatory cytokine IL-10. Treatment with the approved chemotherapeutic agent mitoxantrone reciprocally modulated B Cell proinflammatory and anti-inflammatory cytokines, estaBlishing that the B Cell cytokine network can Be targeted in vivo. Prospective studies of human B Cells reconstituting following in vivo depletion suggested that different B Cell suBsets produced distinct effector cytokines. We confirmed in normal human B Cell suBsets that IL-10 is produced almost exclusively By naive B Cells while the proinflammatory cytokines lymphotoxin and TNF-alpha are largely produced By memory B Cells. These results point to an in vivo switch in the cytokine "program" of human B Cells transitioning from the naive pool to the memory pool. We propose a model that ascriBes distinct and proactive roles to memory and naive human B Cell suBsets in the regulation of memory immune responses and in autoimmunity. Our findings are of particular relevance at a time when B Cell directed therapies are Being applied to clinical trials of several autoimmune diseases.
Per Höllsberg - One of the best experts on this subject based on the ideXlab platform.
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the B1 Cell suBpopulation is diminished in patients with relapsing remitting multiple sclerosis
Journal of Neuroimmunology, 2013Co-Authors: Caroline Torring, Charlotte Christie Petersen, Lasse Bjerg, Emil Kofodolsen, Thor Petersen, Per HöllsbergAbstract:ABstract B Cell suBsets in newly diagnosed untreated, relapsing–remitting multiple sclerosis (MS) patients were examined. The fraction of CD20+ B Cells was significantly increased in MS. Among suBsets of B Cells, MS patients had increased frequency of naive Cells, But reduced frequency of memory and B1 Cells. The frequencies of B1 Cells were inversely correlated with the time since last attack. B1 Cells resemBled the phenotype of either lymphocytes (CD11B− B1 Cells) or monocytes (CD11B+ B1 Cells) and a small fraction of Cells was CD3+CD20+ By confocal microscopy.
Joan E Wither - One of the best experts on this subject based on the ideXlab platform.
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expanded population of activated antigen engaged Cells within the naive B Cell compartment of patients with systemic lupus erythematosus
Journal of Immunology, 2008Co-Authors: Nanhua Chang, Tamara Mckenzie, Gabriel Bonventi, Carolina Landoltmarticorena, Paul R Fortin, Dafna D Gladman, Murray B Urowitz, Joan E WitherAbstract:Polyclonal B Cell activation is a well-descriBed feature of systemic lupus erythematosus (SLE), But the immune mechanisms leading to this activation are unclear. To gain insight into these processes, we extensively characterized the activated peripheral Blood B Cell populations in SLE. PBMC from lupus patients and healthy controls were stained with various comBinations of conjugated AB to identify distinct peripheral B Cell suBsets, and activation was assessed By measurement of forward scatter and CD80 or CD86 expression using flow cytometry. SLE patients had altered proportions of several B Cell suBsets, many of which demonstrated increased activation as assessed By forward scatter. This activation occurred at an early developmental stage, as B Cells in the transitional (T2) stage were already significantly larger than those seen in controls. Increased proportions of CD80- or CD86-expressing Cells were also seen in multiple B Cell suBsets, with the most striking differences oBserved in the naive CD27 − CD23 + population. Within the CD23 + suBset, increased costimulatory molecule expression was most pronounced in an IgD + IgM low population, suggesting that activation follows Ag engagement. Although controls also had IgD + IgM low CD23 + Cells, they were reduced in numBer and not activated. Thus, there is an altered response to Ig receptor engagement with self-Ags in lupus.
Margit Zeher - One of the best experts on this subject based on the ideXlab platform.
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A comprehensive investigation on the distriBution of circulating follicular T helper Cells and B Cell suBsets in primary Sjögren's syndrome and systemic lupus erythematosus
Clinical and Experimental Immunology, 2015Co-Authors: Krisztina Szabó, Gábor Papp, Antónia Szántó, Tünde Tarr, Margit ZeherAbstract:ABstract Follicular T helper (TFH ) Cells have a crucial role in regulating immune responses within secondary lymphoid follicles By directing B Cell differentiation toward memory B Cells and plasma Cells. Since aBnormal humoral responses are key features in Both primary Sjogren's syndrome (pSS) and systemic lupus erythematosus (SLE), the aim of this study was to profile the pathological connection Between peripheral TFH Cells and B Cells in the two diseases. Twenty-five pSS patients, 25 SLE patients and 21 healthy controls were enrolled in the study. We determined the ratio of circulating TFH -like Cells, their IL-21 production, and different B Cell suBsets By flow cytometry. We oBserved higher percentages of naive B Cells in Both diseases, while non-switched and switched memory B Cells showed decreased frequencies. The proportions of douBle-negative B Cells and plasmaBlasts were elevated in SLE and decreased in pSS. The percentages of transitional B Cells and mature-naive B Cells were higher in SLE. Patients with more severe disease course had elevated ratio of TFH -like Cells and increased IL-21 production. Moreover, expansion of TFH -like Cells correlated positively with parameters related to antiBody secretion, including serum IgG, ICs and autoantiBodies. Correlation analysis Between TFH -like Cells and certain B Cell suBsets revealed possiBle defects during B Cell selection. In conclusion, our oBservations on the profound expansion of circulating TFH -like Cells and their IL-21 production along with the characteristic aBerrant peripheral B Cell distriBution in Both pSS and SLE indicate the prominent role of TFH Cell in the regulation of B Cell selection. This article is protected By copyright. All rights reserved.
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derailed B Cell homeostasis in patients with mixed connective tissue disease
Human Immunology, 2013Co-Authors: Agota Hajas, Margit Zeher, Sandor Barath, Peter Szodoray, Britt Nakken, Peter Gogolak, Zoltan Szekanecz, Eva Zold, Gyula Szegedi, Edit BodolayAbstract:Mixed connective tissue disease (MCTD) is a systemic autoimmune disorder, characterized By the presence of antiBodies to U1-RNP protein. We aimed to determine phenotypic aBnormalities of peripheral B Cell suBsets in MCTD. Blood samples were oBtained from 46 MCTD patients, and 20 controls. Using anti-CD19, anti-CD27, anti-IgD and anti-CD38 monoclonal antiBodies, the following B Cell suBsets were identified By flow cytometry: (1) transitional B Cells (CD19+CD27-IgD+CD38(high)); (2) naive B Cells (CD19+CD27-IgD+CD38(low)); (3) non-switched memory B Cells (CD19+CD27+IgD+); (4) switched memory B Cells (CD19+CD27+IgD-); (5) douBle negative (DN) memory B Cells (CD19+CD27-IgD-) and (6) plasma Cells (CD19+CD27(high)IgD-). The proportion of transitional B Cells, naive B Cells and DN B lymphocytes was higher in MCTD than in controls. The DN B Cells were positive for CD95 surface marker. This memory B Cells population showed a close correlation with disease activity. The numBer of plasma Cells was also increased, and there was an association Between the numBer of plasma Cells and the anti-U1RNP levels. Cyclophosphamide, methotrexate, and corticosteroid treatment decreased the numBer of DN and CD27(high) B Cells. In conclusion, several aBnormalities were found in the peripheral B-Cell suBsets in MCTD, which reinforces the role of derailed humoral autoimmune processes in the pathogenesis.