Ex VivoProgramming of Antigen-Presenting B Lymphocytes: Considerations on DNA Uptake and Cell Activation

2006 ◽  
Vol 25 (3-4) ◽  
pp. 83-97 ◽  
Author(s):  
Matthew Wheeler ◽  
Xotchil Cortez-Gonzalez ◽  
Raffaele Frazzi ◽  
Maurizio Zanetti
Keyword(s):  
B Lymphocytes ◽  
Cell Activation ◽  
Dna Uptake ◽  
Antigen Presenting

scholarly journals The B7-2 (B70) costimulatory molecule expressed by monocytes and activated B lymphocytes is the CD86 differentiation antigen

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1402-1407 ◽  
Author(s):  
P Engel ◽  
JG Gribben ◽  
GJ Freeman ◽  
LJ Zhou ◽  
Y Nozawa ◽  
...  
Keyword(s):  
T Cell ◽  
B Lymphocytes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Costimulatory Molecule ◽  
Cell Receptor ◽  
Differentiation Antigen ◽  
Functional Assays ◽  
Antigen Presenting ◽  
Cluster Of Differentiation

Abstract T-cell activation is initiated after T-cell receptor binding to antigen, but also requires interactions between costimulatory molecules expressed on antigen-presenting cells. An important costimulatory molecule expressed by monocytes and activated B lymphocytes has been recently identified and termed B7–2 or B70. Independently, a new Cluster of Differentiation was defined in the Fifth International Leukocyte Differentiation Antigen Workshop as CD86, a molecule predominantly expressed by monocytes and activated B lymphocytes. In this study, the two monoclonal antibodies that defined CD86, FUN-1 and BU-63, were shown to bind to cDNA transfected cells expressing B7– 2/B70. The FUN-1 monoclonal antibody also completely blocked the costimulatory activity of B7–2/B70 in functional assays. Therefore, the serologically defined CD86 differentiation antigen is the B7–2/B70 molecule.

scholarly journals The B7-2 (B70) costimulatory molecule expressed by monocytes and activated B lymphocytes is the CD86 differentiation antigen

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1402-1407 ◽  
Author(s):  
P Engel ◽  
JG Gribben ◽  
GJ Freeman ◽  
LJ Zhou ◽  
Y Nozawa ◽  
...  
Keyword(s):  
T Cell ◽  
B Lymphocytes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Costimulatory Molecule ◽  
Cell Receptor ◽  
Differentiation Antigen ◽  
Functional Assays ◽  
Antigen Presenting ◽  
Cluster Of Differentiation

T-cell activation is initiated after T-cell receptor binding to antigen, but also requires interactions between costimulatory molecules expressed on antigen-presenting cells. An important costimulatory molecule expressed by monocytes and activated B lymphocytes has been recently identified and termed B7–2 or B70. Independently, a new Cluster of Differentiation was defined in the Fifth International Leukocyte Differentiation Antigen Workshop as CD86, a molecule predominantly expressed by monocytes and activated B lymphocytes. In this study, the two monoclonal antibodies that defined CD86, FUN-1 and BU-63, were shown to bind to cDNA transfected cells expressing B7– 2/B70. The FUN-1 monoclonal antibody also completely blocked the costimulatory activity of B7–2/B70 in functional assays. Therefore, the serologically defined CD86 differentiation antigen is the B7–2/B70 molecule.

scholarly journals Early Activation of Teleost B Cells in Response to Rhabdovirus Infection

2014 ◽  
Vol 89 (3) ◽  
pp. 1768-1780 ◽  
Author(s):  
Beatriz Abós ◽  
Rosario Castro ◽  
Aitor González Granja ◽  
Jeffrey J. Havixbeck ◽  
Daniel R. Barreda ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Survival ◽  
B Lymphocytes ◽  
Cell Activation ◽  
Significant Inhibition ◽  
Cell Surface Expression ◽  
Viral Hemorrhagic Septicemia Virus ◽  
Type I ◽  
Endosomal Acidification ◽  
Antigen Presenting

ABSTRACTTo date, the response of teleost B cells to specific pathogens has been only scarcely addressed. In this work, we have demonstrated that viral hemorrhagic septicemia virus (VHSV), a fish rhabdovirus, has the capacity to infect rainbow trout spleen IgM-positive (IgM+) cells, although the infection is not productive. Consequently, we have studied the effects of VHSV on IgM+cell functionality, comparing these effects to those elicited by a Toll-like receptor 3 (TLR3) ligand, poly(I·C). We found that poly(I·C) and VHSV significantly upregulated TLR3 and type I interferon (IFN) transcription in spleen and blood IgM+cells. Further effects included the upregulated transcription of the CK5B chemokine. The significant inhibition of some of these effects in the presence of bafilomycin A1 (BAF), an inhibitor of endosomal acidification, suggests the involvement of an intracellular TLR in these responses. In the case of VHSV, these transcriptional effects were dependent on viral entry into B cells and the initiation of viral transcription. VHSV also provoked the activation of NF-κB and the upregulation of major histocompatibility complex class II (MHC-II) cell surface expression on IgM+cells, which, along with the increased transcription of the costimulatory molecules CD80/86 and CD83, pointed to VHSV-induced IgM+cell activation toward an antigen-presenting profile. Finally, despite the moderate effects of VHSV on IgM+cell proliferation, a consistent effect on IgM+cell survival was detected.IMPORTANCEInnate immune responses to pathogens established through their recognition by pattern recognition receptors (PRRs) have been traditionally ascribed to innate cells. However, recent evidence in mammals has revealed that innate pathogen recognition by B lymphocytes is a crucial factor in shaping the type of immune response that is mounted. In teleosts, these immediate effects of viral encounter on B lymphocytes have not been addressed to date. In our study, we have demonstrated that VHSV infection provoked immediate transcriptional effects on B cells, at least partially mediated by intracellular PRR signaling. VHSV also activated NF-κB and increased IgM+cell survival. Interestingly, VHSV activated B lymphocytes toward an antigen-presenting profile, suggesting an important role of IgM+cells in VHSV presentation. Our results provide a first description of the effects provoked by fish rhabdoviruses through their early interaction with teleost B cells.

Polyclonal activation of B lymphocytes during experimental infection with Schistosoma mansoni

Parasitology ◽  
1990 ◽  
Vol 100 (1) ◽  
pp. 83-91 ◽  
Author(s):  
L. M. Lopes ◽  
M. A. C. Pereira ◽  
S. E. Gerken ◽  
N. Vaz
Keyword(s):  
Schistosoma Mansoni ◽  
B Lymphocytes ◽  
Experimental Infection ◽  
Adoptive Transfer ◽  
Cell Activation ◽  
Protein A ◽  
B Cell Activation ◽  
Spleen Cells ◽  
Polyclonal Activation ◽  
Immunoglobulin Isotypes

SummaryA significant polyclonal activation of B lymphocytes was observed during experimental infection of C57BL/10J mice with Schistosoma mansoni. The isotypic pattern of this expansion, assessed by the Protein-A plaque-forming cell method, was compared with and found to differ from those occurring after infection by Trypanosoma cruzi or injection of bacterial LPS. In the infection of S. mansoni an early expansion of most immunoglobulin isotypes occurs together with a late, sustained expansion of IgG1-secreting cells. High levels of polyclonal B cell activation were observed after adoptive transfer of spleen cells from infected mice to isogenic recipients pre-treated with hydroxyurea.

scholarly journals AB0024 IN VITRO CHARACTERIZATION OF CENERIMOD, A POTENT AND SELECTIVE SPHINGOSINE 1-PHOSPHATE RECEPTOR 1 (S1P1) MODULATOR IN PREVENTING MIGRATION OF NON-ACTIVATED AND ACTIVATED PRIMARY HUMAN B CELLS IN THE PRESENCE OR ABSENCE OF GLUCOCORTICOIDS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1046.1-1046
Author(s):  
L. Schlicher ◽  
P. Kulig ◽  
M. Murphy ◽  
M. Keller
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Activation ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
B Cell Activation ◽  
Human B Cells ◽  
Circulating Lymphocytes

Background:Cenerimod is a potent, selective, and orally active sphingosine 1-phosphate receptor 1 (S1P1) modulator that is currently being evaluated in a Phase 2b study in patients with systemic lupus erythematosus (SLE) (NCT03742037). S1P1 receptor modulators sequester circulating lymphocytes within lymph nodes, thereby reducing pathogenic autoimmune cells (including B lymphocytes) in the blood stream and in inflamed tissues. Extensive clinical experience has become available for the nonselective S1P receptor modulator fingolimod in relapsing forms of multiple sclerosis, supporting this therapeutic concept for the treatment of autoimmune disorders.Objectives:Although the effect of S1P-receptor modulators in reducing peripheral B cells is well documented1,2, the role of the S1P1 receptor on this cell type is only incompletely understood. In this study, the mode of action of cenerimod on primary human B cells was investigated in a series of in vitro experiments, including S1P1 receptor cell surface expression and chemotaxis towards S1P. Moreover, S1P1 expression following B cell activation in vitro was studied. As glucocorticoids (GC) are frequently used in the treatment of patients with autoimmune disorders including SLE, the potential influence of GC on the mode of action of cenerimod was evaluated.Methods:Primary human B lymphocytes from healthy donors were isolated from whole blood. In one set of experiments, cells were treated with different concentrations of cenerimod to measure S1P1 receptor internalization by flow cytometry. In a second set of experiments, isolated B cells were activated using different stimuli or left untreated. Cells were then analysed for S1P1 and CD69 cell surface expression and tested in a novel real-time S1P-mediated migration assay. In addition, the effect of physiological concentrations of GCs (prednisolone and prednisone) on cenerimod activity in preventing S1P mediated migration was tested.Results:In vitro, cenerimod led to a dose-dependent internalization of the S1P1 receptor on primary human B lymphocytes. Cenerimod also blocked migration of nonactivated and activated B lymphocytes towards S1P in a concentration-dependent manner, which is in line with the retention of lymphocytes in the lymph node and the reduction of circulating lymphocytes observed in the clinical setting. Upon B cell activation, which was monitored by CD69 upregulation, a simultaneous downregulation of S1P1 expression was detected, leading to less efficient S1P-directed cell migration. Importantly, physiological concentrations of GC did not affect the inhibitory activity of cenerimod on B cell migration.Conclusion:These results show that cenerimod, by modulating S1P1, blocks B lymphocyte migration towards its natural chemoattractant S1P and demonstrate compatibility of cenerimod with GC. These results are consistent with results of comparable experiments done previously using primary human T lymphocytes.References:[1]Nakamura M et al., Mult Scler. 2014 Sep; 20(10):1371-80.[2]Strasser DS et al., RMD Open 2020;6:e001261.Disclosure of Interests:None declared

scholarly journals Damage-Associated Molecular Patterns Modulation by microRNA: Relevance on Immunogenic Cell Death and Cancer Treatment Outcome

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2566
Author(s):  
María Julia Lamberti ◽  
Annunziata Nigro ◽  
Vincenzo Casolaro ◽  
Natalia Belén Rumie Vittar ◽  
Jessica Dal Col
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Cell Activation ◽  
Adaptive Immune Response ◽  
Current Status ◽  
Immunogenic Cell Death ◽  
Basal Expression ◽  
Antigen Presenting ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Immunogenic cell death (ICD) in cancer is a functionally unique regulated form of stress-mediated cell death that activates both the innate and adaptive immune response against tumor cells. ICD makes dying cancer cells immunogenic by improving both antigenicity and adjuvanticity. The latter relies on the spatiotemporally coordinated release or exposure of danger signals (DAMPs) that drive robust antigen-presenting cell activation. The expression of DAMPs is often constitutive in tumor cells, but it is the initiating stressor, called ICD-inducer, which finally triggers the intracellular response that determines the kinetics and intensity of their release. However, the contribution of cell-autonomous features, such as the epigenetic background, to the development of ICD has not been addressed in sufficient depth. In this context, it has been revealed that several microRNAs (miRNAs), besides acting as tumor promoters or suppressors, can control the ICD-associated exposure of some DAMPs and their basal expression in cancer. Here, we provide a general overview of the dysregulation of cancer-associated miRNAs whose targets are DAMPs, through which new molecular mediators that underlie the immunogenicity of ICD were identified. The current status of miRNA-targeted therapeutics combined with ICD inducers is discussed. A solid comprehension of these processes will provide a framework to evaluate miRNA targets for cancer immunotherapy.

scholarly journals A role for CD9 molecules in T cell activation.

1996 ◽  
Vol 184 (2) ◽  
pp. 753-758 ◽  
Author(s):  
X G Tai ◽  
Y Yashiro ◽  
R Abe ◽  
K Toyooka ◽  
C R Wood ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Expression Cloning ◽  
Wild Type ◽  
Almost All ◽  
Antigen Presenting ◽  
Deficient Mice

Costimulation mediated by the CD28 molecule plays an important role in optimal activation of T cells. However, CD28-deficient mice can mount effective T cell-dependent immune responses, suggesting the existence of other costimulatory systems. In a search for other costimulatory molecules on T cells, we have developed a monoclonal antibody (mAb) that can costimulate T cells in the absence of antigen-presenting cells (APC). The molecule recognized by this mAb, 9D3, was found to be expressed on almost all mature T cells and to be a protein of approximately 24 kD molecular mass. By expression cloning, this molecule was identified as CD9, 9D3 (anti-CD9) synergized with suboptimal doses of anti-CD3 mAb in inducing proliferation by virgin T cells. Costimulation was induced by independent ligation of CD3 and CD9, suggesting that colocalization of these two molecules is not required for T cell activation. The costimulation by anti-CD9 was as potent as that by anti-CD28. Moreover, anti-CD9 costimulated in a CD28-independent way because anti-CD9 equally costimulated T cells from the CD28-deficient as well as wild-type mice. Thus, these results indicate that CD9 serves as a molecule on T cells that can deliver a potent CD28-independent costimulatory signal.

scholarly journals Lipid raft–dependent plasma membrane repair interferes with the activation of B lymphocytes

2015 ◽  
Vol 211 (6) ◽  
pp. 1193-1205 ◽  
Author(s):  
Heather Miller ◽  
Thiago Castro-Gomes ◽  
Matthias Corrotte ◽  
Christina Tam ◽  
Timothy K. Maugel ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
B Cell ◽  
B Lymphocytes ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Cell Activation ◽  
Dependent Manner ◽  
B Cell Activation ◽  
Membrane Repair ◽  
Membrane Injury

Cells rapidly repair plasma membrane (PM) damage by a process requiring Ca2+-dependent lysosome exocytosis. Acid sphingomyelinase (ASM) released from lysosomes induces endocytosis of injured membrane through caveolae, membrane invaginations from lipid rafts. How B lymphocytes, lacking any known form of caveolin, repair membrane injury is unknown. Here we show that B lymphocytes repair PM wounds in a Ca2+-dependent manner. Wounding induces lysosome exocytosis and endocytosis of dextran and the raft-binding cholera toxin subunit B (CTB). Resealing is reduced by ASM inhibitors and ASM deficiency and enhanced or restored by extracellular exposure to sphingomyelinase. B cell activation via B cell receptors (BCRs), a process requiring lipid rafts, interferes with PM repair. Conversely, wounding inhibits BCR signaling and internalization by disrupting BCR–lipid raft coclustering and by inducing the endocytosis of raft-bound CTB separately from BCR into tubular invaginations. Thus, PM repair and B cell activation interfere with one another because of competition for lipid rafts, revealing how frequent membrane injury and repair can impair B lymphocyte–mediated immune responses.

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