Platelet Membranes/Drug Combination as Antigenic Stimulus for Lymphocytes of Patients with Autoimmune Quinine- or Quinidine-Dependent Purpura

1979 ◽  
Author(s):  
P. K. Hosseinzadeh ◽  
B. G. Firkin ◽  
S. L. Pfueller
Keyword(s):  
B Cell ◽  
Drug Combination ◽  
Lymphocyte Transformation ◽  
Pokeweed Mitogen ◽  
Induced Response ◽  
Thymidine Uptake ◽  
Membrane Component ◽  
Igg Antibody ◽  
Drug Induced ◽  
Antigenic Stimulus

Quinine- or quinidine-induced thrombocytopaenia appears due to synthesis of an IgG antibody which causes platelet damage. We have studied the nature of the antigenic stimulus in this disorder by measuring the incorporation of 3H-thymidine into DNA of normal or patients’ lymphocytes cultured in the presence of the drugs in comparison to known mitogens (phytohaemagglutin-P or pokeweed mitogen).’ Patients’ lymphocytes responded normally to mitogens but not to the drugs, heterologous or autologous platelets alone. However, significant thymidine uptake occurred when patients’ lymphocytes were cultured with autologous or heterologous platelets in the presence of therapeutic concentrations of the drugs (2.4 x 10-4 . 2.4 x 10-8M). Lymphocyte transformation was maximal after 7 days (up to 93% of phytohaemagglutinin-induced response), suggesting B cell involvement. Supernatants from platelets which had undergone the release reaction could not replace platelets while membranes were more effective than platelets on-a protein basis. Control lymphocytes from 20 normals and 8 patients with non-drug-induced thrombocytopaenia did not demonstrate transformation by the drugs and platelets. Thus the drug in combination with a platelet membrane component act as an antigenic stimulus only for sensitised lymphocytes.

scholarly journals GENETIC CONTROL OF THE IMMUNE RESPONSE

1974 ◽  
Vol 140 (4) ◽  
pp. 977-994 ◽  
Author(s):  
Peter Lonai ◽  
Hugh O. McDevitt
Keyword(s):  
T Cells ◽  
B Cell ◽  
Tritiated Thymidine ◽  
Lymphocyte Transformation ◽  
Cross Reactivity ◽  
Pokeweed Mitogen ◽  
Thymidine Uptake ◽  
Soluble Antigen

In vitro antigen-induced tritiated thymidine uptake has been used to study the response of sensitized lymphocytes to (T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L in responder and nonresponder strains of mice. The reaction is T-cell and macrophage dependent. Highly purified T cells (91% Thy 1.2 positive) are also responsive, suggesting that this in vitro lymphocyte transformation system is not B-cell dependent. Lymphocytes from high and low responder mice stimulated in vitro react as responders and nonresponders in a pattern identical to that seen with in vivo immunization. Stimulation occurs only if soluble antigen is added at physiological temperatures; antigen exposure at 4°C followed by washing and incubation at 37°C fails to induce lymphocyte transformation. Stimulation is specific for the immunizing antigen and does not exhibit the serologic cross-reactivity which is characteristic of these three antigens and their respective antisera. The reaction can be inhibited by anti-H-2 sera but not by anti-immunoglobulin sera. The anti-immunoglobulin sera did, however, inhibit lipopolysaccharide or pokeweed mitogen stimulation. These results suggest that the Ir-1A gene(s) are expressed in T cells, and that there are fundamental physiologic differences between T- and B-cell antigen recognition.

The Nature of Drug-Induced B Cell Tolerance

1979 ◽  
Vol 43 (1) ◽  
pp. 43-68 ◽  
Author(s):  
James G. Howard ◽  
Frank L. Shand
Keyword(s):  
B Cell ◽  
Cell Tolerance ◽  
B Cell Tolerance ◽  
Drug Induced

scholarly journals Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor.

1994 ◽  
Vol 14 (2) ◽  
pp. 1431-1437 ◽  
Author(s):  
B Samal ◽  
Y Sun ◽  
G Stearns ◽  
C Xie ◽  
S Suggs ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Stem Cell Factor ◽  
Human Peripheral Blood ◽  
Biological Activities ◽  
In Vitro Assays ◽  
Pokeweed Mitogen ◽  
Interleukin 7 ◽  
Enhancing Factor ◽  
Cell Colony

A novel gene coding for the pre-B-cell colony-enhancing factor (PBEF) has been isolated from a human peripheral blood lymphocyte cDNA library. The expression of this gene is induced by pokeweed mitogen and superinduced by cycloheximide. It is also induced in the T-lymphoblastoid cell line HUT 78 after phorbol ester (phorbol myristate acetate) treatment. The predominant mRNA for PBEF is approximately 2.4 kb long and codes for a 52-kDa secreted protein. The 3' untranslated region of the mRNA has multiple TATT motifs, usually found in cytokine and oncogene messages. The PBEF gene is mainly transcribed in human bone marrow, liver tissue, and muscle. We have expressed PBEF in COS 7 and PA317 cells and have tested the biological activities of the conditioned medium as well as the antibody-purified protein in different in vitro assays. PBEF itself had no activity but synergized the pre-B-cell colony formation activity of stem cell factor and interleukin 7. In the presence of PBEF, the number of pre-B-cell colonies was increased by at least 70% above the amount stimulated by stem cell factor plus interleukin 7. No effect of PBEF was found with cells of myeloid or erythroid lineages. These data define PBEF as a novel cytokine which acts on early B-lineage precursor cells.

scholarly journals Polymorphisms in B Cell Co-Stimulatory Genes Are Associated with IgG Antibody Responses against Blood–Stage Proteins of Plasmodium vivax

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0149581 ◽  
Author(s):  
Gustavo C. Cassiano ◽  
Adriana A. C. Furini ◽  
Marcela P. Capobianco ◽  
Luciane M. Storti-Melo ◽  
Maristela G. Cunha ◽  
...  
Keyword(s):  
B Cell ◽  
Plasmodium Vivax ◽  
Antibody Responses ◽  
Blood Stage ◽  
Igg Antibody

scholarly journals 808 Tertiary lymphoid structure gene signature detected in immune checkpoint inhibitor-associated renal immune related adverse event

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A845-A845
Author(s):  
Jamie Lin ◽  
Amanda Tchakarov ◽  
Noha Abdel-Wahab ◽  
Houssein Safa ◽  
Salah-Eddine Bentebibel ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Kidney Biopsy ◽  
Marker Gene ◽  
Prognostic Significance ◽  
Acute Interstitial Nephritis ◽  
Differentially Expressed ◽  
Cancer Center ◽  
Induced Response ◽  
And Control

BackgroundTertiary lymphoid structures (TLSs) have been previously associated with ICI induced response in patients with cancer, but a commensurate observation has not been made in ICI associated immune related adverse events (irAEs). Acute interstitial nephritis (AIN) is the predominant lesion reported in patients with renal irAEs, but various etiologies can also trigger the development of AIN including non-ICI drugs (e.g. non-steroidal anti-inflammatory drugs, antibiotics, proton pump inhibitors, etc.), and it is unknown whether these mechanisms are similar. With increasing indications for ICIs in cancer therapy, there is a critical need to define immune pathways driving the emergence of irAEs. To address this critical knowledge gap, we performed gene expression profiling on ICI-AIN, drug-AIN, and control (non-AIN) kidney biopsy specimens.MethodsTotal RNA extracted from ICI-AIN (n = 6), drug-AIN (n = 4), and control (n = 4) fixed formalin paraffin embedded archival kidney biopsy samples was analyzed by Nanostring nCounter PanCancer Immune Profiling Panel using NanoString nCounter FLEX Analysis System.ResultsThree comparisons were conducted: ICI-AIN vs control, drug-AIN vs control, and ICI-AIN vs drug-AIN. A total of 147 genes were differentially expressed in ICI-AIN vs control and the most differentially expressed genes were CXCL 9, 10, and 11. Similarly, cell marker gene expression signatures (GES) revealed significant upregulation of T and B cell markers in ICI-AIN vs control (P < 0.01) and ICI-AIN vs drug-AIN (T cell P < 0.05; B cell P < 0.01). Differences in T and B cell score were not detected in drug-AIN vs control. Since irAEs have been associated with anti-tumor efficacy, we investigated whether a TLS signature could be detected in ICI-AIN using a four GES (CD79A, MS4A1, LAMP3 and POU2AF1). The ICI-AIN group had significantly higher TLS score compared to both control and drug-AIN groups. Since several TLS signatures have been reported, we also calculated a 12-chemokine TLS GES which was also found to be statistically significant (P < 0.05). Th1 and Th17 cells have been associated with the formation of TLS, differential upregulation of Th1 associated genes but not Th17 associated genes were detected. Furthermore, differential expression IFN-y and TNF signature was also observed in ICI-AIN group.ConclusionsThis study is the first to demonstrate the presence of TLS immune signature in irAEs. Further investigations into the prognostic significance and strategies to uncouple ICI-associated anti-tumor benefits from ICI-induced irAEs should be explored.Ethics ApprovalThe study was approved by The University of Texas MD Anderson Cancer Center intuition's Ethics Board, approval number PA16-1016

Surface markers of cloned human T cells with helper or suppressor activity on pokeweed mitogen-driven B cell differentiation

1982 ◽  
Vol 12 (10) ◽  
pp. 900-903 ◽  
Author(s):  
Maria Cristina Mingari ◽  
Giovanni Melioli ◽  
Alessandro Moretta ◽  
Giuseppe Pantaleo ◽  
Lorenzo Moretta
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
B Cell ◽  
Pokeweed Mitogen ◽  
Surface Markers ◽  
B Cell Differentiation ◽  
Suppressor Activity ◽  
Human T Cells

scholarly journals KCTD15 is overexpressed in human childhood B-cell acute lymphoid leukemia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Giovanni Smaldone ◽  
Giuliana Beneduce ◽  
Mariarosaria Incoronato ◽  
Katia Pane ◽  
Monica Franzese ◽  
...  
Keyword(s):  
B Cell ◽  
Molecular Mechanisms ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Pokeweed Mitogen ◽  
Pathological State ◽  
Lymphoid Leukemia ◽  
Continuous Cell Lines ◽  
Tetramerization Domain

AbstractLeukemic cells originate from the malignant transformation of undifferentiated myeloid/lymphoid hematopoietic progenitors normally residing in bone marrow. As the precise molecular mechanisms underlying this heterogeneous disease are yet to be disclosed, the identification and the validation of novel actors in leukemia is of extreme importance. Here, we show that KCTD15, a member of the emerging class of KCTD ((K)potassium Channel Tetramerization Domain containing) proteins, is strongly upregulated in patients affected by B-cell type acute lymphoblastic leukemia (B-ALL) and in continuous cell lines (RS4;11, REH, TOM-1, SEM) derived from this form of childhood leukemia. Interestingly, KCTD15 downregulation induces apoptosis and cell death suggesting that it has a role in cellular homeostasis and proliferation. In addition, stimulation of normal lymphocytes with the pokeweed mitogen leads to increased KCTD15 levels in a fashion comparable to those observed in proliferating leukemic cells. In this way, the role of KCTD15 is likely not confined to the B-ALL pathological state and extends to activation and proliferation of normal lymphocytes. Collectively, data here presented indicate that KCTD15 is an important and hitherto unidentified player in childhood lymphoid leukemia, and its study could open a new scenario for the identification of altered and still unknown molecular pathways in leukemia.

scholarly journals Pathway Interactions Based on Drug-Induced Datasets

2019 ◽  
Vol 18 ◽  
pp. 117693511985151 ◽  
Author(s):  
Shinuk Kim
Keyword(s):  
Breast Cancer ◽  
Valproic Acid ◽  
Epithelial Cells ◽  
Sample Size ◽  
Drug Combination ◽  
Trichostatin A ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Drug Induced

In this study, we identified enrichment pathway connections from MCF7 breast cancer epithelial cells that were treated with 87 drugs. We extracted drug-treated samples, where the sample size was greater than or equal to 5. The drugs included 17-allylamino-geldanamycin, LY294002, trichostatin A, valproic acid, sirolimus, and wortmannin, which had sample sizes of 11, 8, 7, 7, 7, and 5, respectively. We found meaningful pathways using gene set enrichment analysis and identified intradrug and interdrug pathway interactions, which implied the influence of drug combination. Among the top 20 enrichment pathways that were wortmannin induced, there were a total of 37 intradrug pathway interactions via common genes. Thirty-seven pathway interactions were induced by valproic acid, 11 induced by trichostatin A, 20 induced by LY294002, and 59 induced by sirolimus, all via common genes. The number of interdrug-induced pathway interactions ranged from one pair of pathways to 23. The pair of ERBB_SIGNALING and INSULIN_SIGNALING pathways showed the highest score from a pair of 2 individual drugs. The highest number of pathway interactions was observed between the drugs 17-allylamino-geldanamycin and LY294002.

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