Analysis of CD20 and PD-L1 levels on small extracellular vesicles (sEV) produced by DLBCL cells and EBV-transformed B cells, and potential role in T cell inhibition.

Increasing evidence supports a role for small extracellular vesicles (sEV, including exosomes) in Diffuse Large B-cell lymphoma (DLBCL) progression and resistance to treatment. CD20 and PD-L1 are found on DLBCL-derived sEV, but little is known about their patient-level heterogeneity. Moreover, the capacity of PD-L1 sEV to modulate T cells needs to be clarified.

Anti-Proliferative and Pro-Apoptotic vLMW Fucoidan Formulas Decrease PD-L1 Surface Expression in EBV Latency III and DLBCL Tumoral B-Cells by Decreasing Actin Network.

Epstein-Barr virus (EBV) infects 95% of the world's population and persists latently in the body. It immortalizes B-cells and is associated with lymphomas. LCLs (lymphoblastoid cell lines, EBV latency III B-cells) inhibit anti-tumoral T-cell response following PD-L1 overexpression (programmed death-ligand 1 immune checkpoint).

Alternative mRNA Transcripts as an Additional Tool for c-Myc2 and c-MycS Production in BL60 Tumors.

While studying c-Myc protein expression in several Burkitt lymphoma cell lines and in lymph nodes from a mouse model bearing a translocated gene from the human BL line IARC-BL60, we surprisingly discovered a complex electrophoretic profile. Indeed, the BL60 cell line carrying the (8;22) translocation exhibits a simple pattern, with a single c-Myc2 isoform. Analysis of the transcripts expressed by tumor lymph nodes in the mouse () showed for the first time five transcripts that are associated with (8;22) translocation.

CD20 expression, TrkB activation and functional activity of diffuse large B cell lymphoma-derived small extracellular vesicles.

Background: Small extracellular vesicles (sEVs) including exosomes, carrying the CD20, could be involved in immunotherapy resistance in diffuse large B cell lymphoma (DLBCL). We have reported endogenous brain-derived neurotrophic factor/TrkB (tropomyosin-related kinase B) survival axis in DLBCL. Here, we performed a comparative study of sEV production by germinal centre B cell (GCB) and activated B cell (ABC)-DLBCL cell lines, and analysed TrkB activation on this process.

c-Rel Is the Pivotal NF-κB Subunit in Germinal Center Diffuse Large B-Cell Lymphoma: A LYSA Study.

Relationships between c-Rel and GCB-DLBCLs remain unclear. We found that strong c-Rel DNA-binding activity was mostly found in GCBs on two independent series of 48 DLBCLs and 66 DLBCLs, the latter issued from the GHEDI series. c-Rel DNA-binding activity was associated with increased mRNA expression.

Prohibitin (PHB) expression is associated with aggressiveness in DLBCL and flavagline-mediated inhibition of cytoplasmic PHB functions induces anti-tumor effects.

Background: Diffuse large B-cell lymphomas (DLBCLs) are aggressive lymphomas accounting for approximately a third of non-Hodgkin lymphomas. Prohibitin 1 (PHB1) and prohibitin 2 (PHB2) are scaffold proteins that promote mitochondria homeostasis and consequently cell survival, but biological functions of cytoplasmic PHBs remain largely unknown in DLBCL.

Methods: PHB expression was analyzed in 82 DLBCL biopsies and five DLBCL cell lines by immunohistochemistry (IHC) and Western blotting.

Anti-apoptotic role and clinical relevance of neurotrophins in diffuse large B-cell lymphomas.

Background: Diffuse large B-cell lymphoma (DLBCL) is a fatal malignancy that needs to identify new targets for additional therapeutic options. This study aimed to clarify the clinical and biological significance of endogenous neurotrophin (nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)) in DLBCL biopsy samples and cell lines.

Methods: We analysed expression of NGF, BDNF, and their receptors (Trk, p75(NTR)) in 51 biopsies and cell lines by immunohistochemistry, immunofluorescence, and western blotting.

Differential expression of neurotensin and specific receptors, NTSR1 and NTSR2, in normal and malignant human B lymphocytes.

Neurotensin, a neuropeptide growth factor, and its two specific neurotensin receptors, NTSR1 and NTSR2, were shown to be expressed by human B cell lines. Another NTSR, sortilin, which is common to neurotensin and neurotrophins, was also detected as we have previously described. Neurotensin was functional in B cell lines; it induced their proliferation and inhibited apoptosis induced by serum deprivation or Fas activation.

Endogenous neurotrophins and Trk signaling in diffuse large B cell lymphoma cell lines are involved in sensitivity to rituximab-induced apoptosis.

Background: Diffuse large B-cell lymphoma (DLBCL) is a common and often fatal malignancy. Immunochemotherapy, a combination of rituximab to standard chemotherapy, has resulted in improved survival. However a substantial proportion of patients still fail to reach sustained remission.

Prognostic significance of BAD and AIF apoptotic pathways in diffuse large B-cell lymphoma.

Background: To determine whether proapoptotic proteins were associated with clinicopathologic heterogeneity and influenced survival in patients with diffuse large B-cell lymphoma (DLBCL), we evaluated patterns of expression of the BCL-2 family member BAD, PP1alpha (the catalytic subunit of PP1 involved in activation of BAD), and apoptosis-inducing factor (AIF).

Patients And Methods: We retrospectively analyzed 46 patients all treated with standard chemotherapy ([CHOP] cyclophosphamide/doxorubicin/vincristine/prednisone-like); of these, 16 received rituximab. Immunohistochemical analyses were performed from biopsy samples of nodal DLBCL that were performed at initial diagnosis.

Aged mice exhibit distinct peripheral B-cell phenotypes differing in apoptotic susceptibility: an ex vivo analysis.

Background: Age-related changes in the antibody response have been classically associated with alterations in T-cell help, but increasing evidence shows that intrinsic B-cell defects exist. This article analyzes the apoptotic susceptibility of peripheral B-cells in aged and young control mice.

Materials And Methods: Freshly isolated lymphocytes from spleen and Peyer's patches (PPs) were labeled for B-cell lineage (B220(+) cells) and germinal center B subset (GCs, B220(+)/PNA(+) cells).

Activation of Bad trafficking is involved in the BCR-mediated apoptosis of immature B cells.

The activity of Bad, a pro-apoptotic protein, is regulated by reversible phosphorylation. Moreover, sequestration of Bad within subcellular compartments may be a new mechanism of apoptosis regulation. In this study, we report that Bad interacts with 14-3-3 protein in WEHI-231 immature B cells.

Changes in bad phosphorylation are correlated with BCR-induced apoptosis of WEHI-231 immature B cells.

Signaling through the B cell antigen receptor (BCR) is a key determinant in the regulation of B cell physiology. Depending on additional factors, such as microenvironment and developmental stage, ligation of the BCR can trigger B lymphocyte activation, proliferation, or apoptosis. The regulatory mechanisms determining B cell apoptosis and survival are not completely known.

Dietary vitamin E and rainbow trout (Oncorhynchus mykiss) phagocyte functions: effect on gut and on head kidney leucocytes.

The effects of vitamin E (deficiency or supplementation) on the non-specific immune system in rainbow trout, Oncorhynchus mykiss, were evaluated. Rainbow trout were fed daily a semi-purified diet supplemented with vitamin E at 0, 28 and 295 mg x kg(-1) of diet. After 80 days of experimental feeding, the phagocytic function (respiratory burst evaluated by the CL response, phagocytosis) from gut leucocytes and head kidney enriched macrophages was measured; head kidney cell pinocytosis and serum lysozyme activity were also analysed.

Optimization of cell permeabilization for multiparametric flow cytometric analysis with lectin staining.

Background: This study was undertaken in mice to develop a reproducible procedure of cell permeabilization, allowing intracellular protein staining by immunofluorescence (i.e., Bcl-2) without losing surface labeling especially for lectins (i.

Age-related alterations of somatic hypermutation and CDR3 lengths in human Vkappa4-expressing B lymphocytes.

The lower avidity and/or affinity of antibodies generated by an aged immune system could be attributed to two major changes in the antibody repertoire: a shift in germline gene usage and a decrease in the rate of immunoglobulin hypermutation. In an attempt to identify the mechanisms involved in the observed humoral immune deficiency in the elderly, we studied whether differences in the somatic diversity of a particular Vkappa region occurred with ageing. By using the polymerase chain reaction and sequencing, we analysed and compared Vkappa4-Jkappa rearrangements isolated from young (mean age 21 years) and aged (mean age 83 years) healthy adults.

Modification of HLA expression on peripheral lymphocytes and monocytes during aging.

Immunosenescence involves modifications of humoral and cellular immunity. Here we report the analysis of human leukocyte antigen (HLA) expression on T lymphocytes, B lymphocytes and monocytes of 58 healthy subjects aged 23-95 years old. Using a double staining immunofluorescence and flow cytometry analysis, we have determined the percentages of cells expressing HLA class-I and HLA-DR antigens.

Differential effects of temperature on specific and nonspecific immune defences in fish.

The susceptibility of fish to disease is partly dependent on their environment, in particular on water temperature. It is generally accepted that lower temperatures adversely affect specific immune responses mediated by T helper cells. The probable mechanisms involved in such suppression in teleost fish are reviewed.

Effects and mechanisms of environmental temperature on carp (Cyprinus carpio) anti-DNP antibody response and non-specific cytotoxic cell activity: a kinetic study.

The effect of environmental temperatures on immune competence was investigated in carp which were subjected to changes in water temperature. The activity of non-specific cytotoxic cells (NCC) against P815 target cells, and the anti-DNP antibody response were evaluated until day 56 after transfer. Low environmental temperature (12 +/- 0.

Serotonin modulation of lymphocyte proliferation via 5-HT1A receptors in rainbow trout (Oncorhynchus mykiss).

In this study, the effects of serotonin (5-HT) on in vitro lymphoproliferation in rainbow trout (Oncorhynchus mykiss) are investigated. Serotonin exerted immunosuppressive effects on lipopolysaccharide (LPS) and phytohemagglutinin (PHA)-stimulated proliferation of fish peripheral blood lymphocytes (PBL). 8-OH-DPAT (an agonist of 5-HT1A receptors) mimicked the inhibitory effects of serotonin on lymphocyte proliferation, whereas addition of spiperone (an antagonist of 5-HT1A and 5-HT1B receptors) reversed these inhibitory effects, indicating that 5-HT1A receptors may be implicated in serotonin-induced immunosuppression.

[Antibody response, cortisolemia and prolactinemia in rainbow trouts].

We have studied the humoral immune response (production of anti-Yersinia ruckeri antibodies), and measured the levels of plasmatic hormones (cortisol and prolactin) in rainbow trout (Oncorhynchus mykiss) subjected to hyperosmotic stress (NaCl, 22 / 1000). Under acute stressful conditions (saline stress during 7 days), high blood cortisol and prolactin (PRL) levels were correlated with a weak anti-Yersinia ruckeri antibody response, as evidenced by late and low antibody titres as compared to normal fish. Interestingly, the group of fish subjected to chronic stress (till 30 days) exhibited no significant differences in blood cortisol and prolactin levels despite low antibody titres as compared to control group.

Structure-activity relationship of phenolic compounds (phenol, pyrocatechol and hydroquinone) on natural lymphocytotoxicity of carp (Cyprinus carpio).

We have tested the effects of phenol and two diphenols (pyrocatechol and hydroquinone) on a non-specific immune response, i.e. the natural cytotoxic activity, of the carp.

Nutritional influences on in vitro splenic lymphocyte proliferation in Psammomys obesus (Rodentia Gerbillidae).

The standard laboratory diet administered to sand rat (Psammomys obesus) induces the following physiological and immunological changes: hyperglycemia and hypercholesterolemia involving mainly the free fraction of cholesterol, with an elevation of high-density-lipoprotein levels and a decrease in B and T splenic lymphocyte proliferation in the presence of different mitogens PHA-P, Con A and LPS. These results demonstrate the important modification that could be induced in sand rat by the standard laboratory diet as compared with natural diet, and thus the sand rat (P. obesus) appears to be an interesting model for studies on experimental diabetes mellitus.

Effects of temperature on carp leukocyte mitogen-induced proliferation and nonspecific cytotoxic activity.

The effect of environmental temperature on immune competence was investigated in carp subjected to abrupt changes in water temperature. The activity of nonspecific cytotoxic cells (NCC) against P815 target cells and the lymphoproliferation induced by PHA and ConA were evaluated. Low in vivo temperature (12 +/- 0.