scholarly journals CD83 Modulates B Cell Function In Vitro: Increased IL-10 and Reduced Ig Secretion by CD83Tg B Cells

PLoS ONE ◽  
2007 ◽  
Vol 2 (8) ◽  
pp. e755 ◽  
Author(s):  
Birte Kretschmer ◽  
Katja Lüthje ◽  
Andreas H. Guse ◽  
Svenja Ehrlich ◽  
Friedrich Koch-Nolte ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
B Cell Function

scholarly journals In vitro regulation of immunoglobulin synthesis after marrow transplantation. I. T-cell and B-cell deficiencies in patients with and without chronic graft-versus-host disease

Blood ◽  
1981 ◽  
Vol 58 (3) ◽  
pp. 431-439 ◽  
Author(s):  
LG Lum ◽  
MC Seigneuret ◽  
RF Storb ◽  
RP Witherspoon ◽  
ED Thomas
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Cell Function ◽  
Cell Activity ◽  
Graft Versus Host ◽  
B Cell Function

Abstract Twenty-four patients with aplastic anemia or acute leukemia were treated by marrow grafts from HLA-identical donors after conditioning with high doses of cyclophosphamide and/or today body irradiation. They were studied between 4 and 63 mo (median 14.2) after transplantation. Seventeen patients had chronic graft-versus-host disease (C-GVHD) and 7 were healthy. They were studied for defects in their T- and B-cell function using and indirect hemolytic plaque assay for Ig production after 6 days of culture in the presence of pokeweek mitogen. T or B cells from the patients with or without C-GVHD were cocultured with T or B cells from their HLA-identical marrow donors or unrelated normal controls. Intrinsic B-cell defects, lack of helper T-cell activity, and suppressor T-cell activity were more frequently found in patients with C-GVHD than in healthy patients. Fifteen of the 17 patients with C-GVHD showed on or more defects in their T-and B-cell function compared to only 3 of the 7 patients without C-GVHD. None of the healthy controls, including the marrow donors, showed defects in their T- and B-cell functions. These in vitro findings may be helpful in assessing the process of immune reconstitution and the immunologic aberration found after human marrow transplantation.

scholarly journals In vitro regulation of immunoglobulin synthesis after marrow transplantation. I. T-cell and B-cell deficiencies in patients with and without chronic graft-versus-host disease

Blood ◽  
1981 ◽  
Vol 58 (3) ◽  
pp. 431-439 ◽  
Author(s):  
LG Lum ◽  
MC Seigneuret ◽  
RF Storb ◽  
RP Witherspoon ◽  
ED Thomas
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Cell Function ◽  
Cell Activity ◽  
Graft Versus Host ◽  
B Cell Function

Twenty-four patients with aplastic anemia or acute leukemia were treated by marrow grafts from HLA-identical donors after conditioning with high doses of cyclophosphamide and/or today body irradiation. They were studied between 4 and 63 mo (median 14.2) after transplantation. Seventeen patients had chronic graft-versus-host disease (C-GVHD) and 7 were healthy. They were studied for defects in their T- and B-cell function using and indirect hemolytic plaque assay for Ig production after 6 days of culture in the presence of pokeweek mitogen. T or B cells from the patients with or without C-GVHD were cocultured with T or B cells from their HLA-identical marrow donors or unrelated normal controls. Intrinsic B-cell defects, lack of helper T-cell activity, and suppressor T-cell activity were more frequently found in patients with C-GVHD than in healthy patients. Fifteen of the 17 patients with C-GVHD showed on or more defects in their T-and B-cell function compared to only 3 of the 7 patients without C-GVHD. None of the healthy controls, including the marrow donors, showed defects in their T- and B-cell functions. These in vitro findings may be helpful in assessing the process of immune reconstitution and the immunologic aberration found after human marrow transplantation.

scholarly journals B Cell Receptor Signaling and Protein Kinase D2 Support Regulatory B Cell Function in Pancreatic Cancer

2022 ◽  
Vol 12 ◽  
Author(s):  
Daniel Michaud ◽  
Bhalchandra Mirlekar ◽  
Colleen Steward ◽  
Gail Bishop ◽  
Yuliya Pylayeva-Gupta
Keyword(s):  
Pancreatic Cancer ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
Cell Receptor ◽  
Regulatory B Cell ◽  
B Cell Function ◽  
T Cell Function

B cells can act as potent suppressors of anti-tumor T cell immunity, presenting a mechanism of resistance to immunotherapy. In pancreatic ductal adenocarcinoma, B cells can display a T cell-suppressive or regulatory phenotype centered on the expression of the cytokine Interleukin 35 (IL-35). While B cell-mediated immunosuppression presents a barrier to anti-tumorigenic T cell function, it is not clear how regulatory B cell function could be targeted, and the signals that promote this suppressive phenotype in B cells are not well understood. Here we use a novel IL-35 reporter model to understand which signaling pathways are important for immunosuppressive properties in B cells. In vitro analysis of IL-35 reporter B cells revealed a synergy between the BCR and TLR4 signaling pathways is sufficient to induce IL-35 expression. However, in vivo, B cell receptor activation, as opposed to MyD88 signaling in B cells, is central to B cell-mediated suppression and promotion of pancreatic cancer growth. Further analysis identified protein kinase D2 (PKD2) as being a key downstream regulator of IL-35 expression in B cells. Regulatory B cells with an inactivating mutation in PKD2 failed to produce IL-35 or fully suppress effector T cell function in vitro. Furthermore, inhibition of PKD in B cells decreased tumor growth and promoted effector T cell function upon adoptive transfer into B cell-deficient mice. Collectively, these data provide insight into how regulatory B cell function is promoted in pancreatic cancer and identify potential therapeutic targets to restrain this function.

scholarly journals Metabolomics Analysis of Splenic CD19+ B Cells in Mice Chronically Infected With Echinococcus granulosus sensu lato Protoscoleces

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuxin Guo ◽  
Daxiang Xu ◽  
Zheng Fang ◽  
Shiping Xu ◽  
Jiaxi Liu ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Echinococcus Granulosus ◽  
Cell Function ◽  
Metabolic Reprogramming ◽  
Negative Ion ◽  
Hormone Synthesis ◽  
B Cell Function ◽  
Echinococcus Granulosus Sensu Lato

Background: The larval stages of Echinococcus granulosus sensu lato (E. granulosus s.l) infection can alter B cell function and affect host anti-infective immunity, but the underlying mechanism remains unclear. The newly emerging immunometabolism highlights that several metabolites are key factors in determining the fate of immune cells, which provides a new insight for exploring how larval E. granulosus s.l. infection remodels B cell function. This study investigated the metabolomic profiles of B cells in mice infected with E. granulosus s.l. protoscoleces (PSC).Results:Total CD19+ B cells, purified from the spleen of infected mice, showed significantly increased production of IL-6, TNF-α, and IL-10 after exposure to LPS in vitro. Moreover, the mRNA expression of metabolism related enzymes in B cells was remarkably disordered post infection. In addition, differential metabolites were identified in B cells after infection. There were 340 differential metabolites (83 upregulated and 257 downregulated metabolites) identified in the positive ion model, and 216 differential metabolites (97 upregulated and 119 downregulated metabolites) identified in the negative ion mode. Among these, 64 differential metabolites were annotated and involved in 68 metabolic pathways, including thyroid hormone synthesis, the metabolic processes of glutathione, fructose, mannose, and glycerophospholipid. Furthermore, several differential metabolites such as glutathione, taurine, and inosine were validated to regulate the cytokine production in LPS stimulated B cells.Conclusion:Infection with the larval E. granulosus s.l. causes metabolic reprogramming in the intrinsic B cells of mice, which provides the first evidence for understanding the role and mechanism of B cells in parasite anti-infective immunity from the viewpoint of immunometabolism.

scholarly journals Anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation for B-cell non-Hodgkin's lymphoma: phenotypic reconstitution and B-cell function

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2203-2211 ◽  
Author(s):  
A Pedrazzini ◽  
AS Freedman ◽  
J Andersen ◽  
L Heflin ◽  
K Anderson ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
B Cell Function ◽  
Normal Percentage ◽  
Autologous Bone

In the present report we have attempted to examine immunologic reconstitution following high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MoAb)-purged autologous bone marrow transplantation (ABMT). By cell-surface phenotypic analysis, the majority of patients had normal percentage of natural killer cells (NK), monocytes, and CD8+ T cells at one month post-ABMT. In contrast, the percentage of CD4+ T cells was reduced for at least 3 years, and the CD4:CD8 ratio reflected this imbalance. B-cell reconstitution was slightly prolonged, with normal percentage and absolute numbers of CD20+ B cells evident by 3 months. Although B cells returned by 3 months, in vitro assessment of B-cell function demonstrated impairment of proliferative responses to either anti-immunoglobulins bound to beads (anti-Ig), Epstein-Barr virus (EBV), or interleukin-2 (IL-2) for approximately 1 year and low molecular B-cell growth factor (BCGF) for approximately 2 or more years. Moreover, in vivo B-cell reconstitution demonstrated a more selective defect, with normal levels of immunoglobulin IgM returning at 6 months, IgG at 12 months, and IgA after 2 years. Despite normal numbers of B cells and relative normal levels of Ig early following ABMT, our in vitro data suggest an intrinsic defect in B-cell responsiveness. Moreover, these defects are similar to those observed following nonpurged autologous and allogeneic BMT, although the interval of immune impairment appears more prolonged.

scholarly journals Anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation for B-cell non-Hodgkin's lymphoma: phenotypic reconstitution and B-cell function

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2203-2211 ◽  
Author(s):  
A Pedrazzini ◽  
AS Freedman ◽  
J Andersen ◽  
L Heflin ◽  
K Anderson ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
B Cell Function ◽  
Normal Percentage ◽  
Autologous Bone

Abstract In the present report we have attempted to examine immunologic reconstitution following high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MoAb)-purged autologous bone marrow transplantation (ABMT). By cell-surface phenotypic analysis, the majority of patients had normal percentage of natural killer cells (NK), monocytes, and CD8+ T cells at one month post-ABMT. In contrast, the percentage of CD4+ T cells was reduced for at least 3 years, and the CD4:CD8 ratio reflected this imbalance. B-cell reconstitution was slightly prolonged, with normal percentage and absolute numbers of CD20+ B cells evident by 3 months. Although B cells returned by 3 months, in vitro assessment of B-cell function demonstrated impairment of proliferative responses to either anti-immunoglobulins bound to beads (anti-Ig), Epstein-Barr virus (EBV), or interleukin-2 (IL-2) for approximately 1 year and low molecular B-cell growth factor (BCGF) for approximately 2 or more years. Moreover, in vivo B-cell reconstitution demonstrated a more selective defect, with normal levels of immunoglobulin IgM returning at 6 months, IgG at 12 months, and IgA after 2 years. Despite normal numbers of B cells and relative normal levels of Ig early following ABMT, our in vitro data suggest an intrinsic defect in B-cell responsiveness. Moreover, these defects are similar to those observed following nonpurged autologous and allogeneic BMT, although the interval of immune impairment appears more prolonged.

scholarly journals B-cell proliferative and differentiative responses after autologous peripheral blood stem cell or bone marrow transplantation

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 672-678 ◽  
Author(s):  
S Kiesel ◽  
A Pezzutto ◽  
G Moldenhauer ◽  
R Haas ◽  
M Korbling ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Cell Function ◽  
Peripheral Blood Stem Cell ◽  
Normal Subjects ◽  
B Cell Function

Abstract In this study the authors have evaluated B-cell function after autologous peripheral-blood stem cell transplantation (ABSCT) and autologous bone marrow (ABMT) transplantation. The B-enriched fractions of peripheral blood from ten normal subjects and 22 autografted patients (11 patients after ABMT, eight patients after ABSCT, and three patients after ABSCT followed by ABMT) were investigated. Time postgrafting ranged from 1 to 34 months. Proliferative responses to anti-mu antibody, Staphylococcus aureus Cowan 1 (SAC), and low molecular weight (mol wt) 12-Kd B-cell growth factor (BCGF) were measured. Differentiative responses to the same factors were assessed by quantifying in vitro immunoglobulin (IgG/IgM) production. The authors found no difference in B-cell function between the ABMT and the ABSCT patient groups. Compared to the B cells of normal subjects, only five out of 22 autografted patients showed a normal proliferative response to all agents used, while nine out of 22 did not respond to any signals. Eight out of 22 patients displayed various defects of B- cell response. However, in vitro IgG/IgM secretion of predominantly IgG subclass was normal in 19 out of 22 patients. This in vitro ability to produce Ig was reflected by the patients' normal serum IgG/IgM levels, whereas serum IgA levels were low. The authors speculate that there may be 2 B-cell populations: the normal in vitro Ig production and in vivo serum IgG may come from the stimulation of a small number of re-infused pre-committed memory B cells while, in parallel, immature B cells develop from autografted hematopoietic progenitor cells.

scholarly journals Immunoglobulin profile and B-cell frequencies are altered with changes in the cellular micro-environment independent of the stimulation conditions

2019 ◽  
Author(s):  
Dannielle K Moore ◽  
Gina R Leisching ◽  
Candice I Snyders ◽  
Andrea Gutschmidt ◽  
Ilana C van Rensburg ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Whole Blood ◽  
Cell Activation ◽  
Cell Function ◽  
Cell Phenotype ◽  
Isolated Cells ◽  
B Cell Function ◽  
Cellular Environment

AbstractB-cells are essential in the defense against Mycobacterium tuberculosis. Studies on isolated cells may not accurately reflect the responses that occur in vivo due to the presence of other cells. This study elucidated the influence of microenvironment complexity on B-cell polarisation and function in the context of TB disease. B-cell function was tested in whole blood, PBMC’s and as isolated cells. The different fractions were stimulated and the B-cell phenotype and immunoglobulin profiles analysed. The immunoglobulin profile and killer B-cell frequencies varied for each of the investigated sample types, while in an isolated cellular environment, secretion of immunoglobulin isotypes IgA, IgG2 and IgG3 was hampered. The differences in the immunoglobulin profile highlight the importance of cell-cell communication for B-cell activation. In contrast, increased frequencies of killer B-cells were observed following cellular isolation, suggesting a biased shift in augmented immune response in vitro. This suggests that humoral B-cell function and development was impaired likely due to a lack of co-stimulatory signals from other cell types. Thus, B-cell function should ideally be studied in a PBMC or whole blood fraction.

B-cell proliferative and differentiative responses after autologous peripheral blood stem cell or bone marrow transplantation

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 672-678 ◽  
Author(s):  
S Kiesel ◽  
A Pezzutto ◽  
G Moldenhauer ◽  
R Haas ◽  
M Korbling ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Cell Function ◽  
Peripheral Blood Stem Cell ◽  
Normal Subjects ◽  
B Cell Function

In this study the authors have evaluated B-cell function after autologous peripheral-blood stem cell transplantation (ABSCT) and autologous bone marrow (ABMT) transplantation. The B-enriched fractions of peripheral blood from ten normal subjects and 22 autografted patients (11 patients after ABMT, eight patients after ABSCT, and three patients after ABSCT followed by ABMT) were investigated. Time postgrafting ranged from 1 to 34 months. Proliferative responses to anti-mu antibody, Staphylococcus aureus Cowan 1 (SAC), and low molecular weight (mol wt) 12-Kd B-cell growth factor (BCGF) were measured. Differentiative responses to the same factors were assessed by quantifying in vitro immunoglobulin (IgG/IgM) production. The authors found no difference in B-cell function between the ABMT and the ABSCT patient groups. Compared to the B cells of normal subjects, only five out of 22 autografted patients showed a normal proliferative response to all agents used, while nine out of 22 did not respond to any signals. Eight out of 22 patients displayed various defects of B- cell response. However, in vitro IgG/IgM secretion of predominantly IgG subclass was normal in 19 out of 22 patients. This in vitro ability to produce Ig was reflected by the patients' normal serum IgG/IgM levels, whereas serum IgA levels were low. The authors speculate that there may be 2 B-cell populations: the normal in vitro Ig production and in vivo serum IgG may come from the stimulation of a small number of re-infused pre-committed memory B cells while, in parallel, immature B cells develop from autografted hematopoietic progenitor cells.

scholarly journals B cell-specific GPR55 deficiency promotes atherosclerosis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Guillamat-Prats ◽  
D Hering ◽  
M Rami ◽  
C Haerdtner ◽  
L Bindila ◽  
...  
Keyword(s):  
Body Weight ◽  
B Cells ◽  
B Cell ◽  
Mrna Expression ◽  
Cell Function ◽  
Metabolic Effects ◽  
Atherosclerotic Plaques ◽  
Funding Source ◽  
Sequencing Analysis ◽  
B Cell Function

Abstract Background Atherosclerosis is accompanied by an imbalance between resolving and pro-inflammatory lipid mediators. Targeting lipid signaling pathways might offer a new anti-inflammatory therapy for improving the clinical outcome in cardiovascular disease patients. We considered lysophosphatidylinositol (LPI) and its receptor G protein-coupled receptor (GPR)55 as a potential modulator of atherosclerosis. Its role in regulating atherosclerosis and B cell function is unknown. Hypothesis We assessed the hypothesis that GPR55 signaling causally affects atherosclerosis and whether it has a specific role in regulating B cell function in this disease. Methods Atherosclerotic plaques were compared between apolipoprotein E deficient (ApoE−/−) and ApoE−/−Gpr55−/− mice after 4 to 16 weeks Western Diet (WD; 0.15% cholesterol; n=12–15 per group). To specifically test the role of B cell GPR55 in atherosclerosis, we generated mixed chimeras by lethally irradiating low density lipoprotein receptor deficient (Ldlr−/−) mice and reconstituting with a mixture of μMT and wildtype (control) or μMT and Gpr55−/− bone marrow cells. Circulating B cells were sorted and bulk RNA sequencing analysis was performed. We performed lipid and immunostainings of murine aortic root plaques, qPCR and ELISA of tissue lysates, as well as multiplex analysis of plasma immunoglobulins. Leukocyte plasma and tissue counts were determined by flow cytometry. Results GPR55 expression in mouse and human atherosclerotic plaques was detected by immunostaining. Furthermore, we confirmed murine Gpr55 mRNA expression on sorted circulating B220+B cells via qPCR, which was higher compared to CD3+ T cells, while CD11+ myeloid cells as well as NK cells had only low Gpr55 mRNA levels. ApoE−/−Gpr55−/− mice had significantly larger plaques after 4&16 weeks WD compared to ApoE−/− controls, with more pronounced body weight increases and higher cholesterol levels at the 16 weeks WD time point. In addition, global Gpr55 deficiency resulted in enhanced aortic pro-inflammatory cytokine mRNA expression (IL-1β, IL-6, TNFα) and a massively upregulated IgG1 plasma levels and increased percentages of splenic germinal center and plasma cells. B-cell RNA-seq analysis showed 460 differential expressed regulated genes in the ApoE−/−Gpr55−/− compared to ApoE−/−. The main pathways affected were calcium ion transport, immunoglobulin production, negative regulation of phosphorylation, and cellular component morphogenesis, suggesting a dsysregulation of B cell function. B cell specific Gpr55 deficiency blunted the metabolic effects on body weight and cholesterol, but still translated in larger atherosclerotic plaques and elevated plasma IgG levels compared to the respective controls. Conclusion Both global and B cell-restricted Gpr55 deficiency promotes atherosclerosis and is associated with a more pro-inflammatory phenotype. Our findings suggest a novel role for GPR55 in regulating B cell development and function. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft (DFG)

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