scholarly journals Identification and Characterization of a Germline Mutation in CARD11 From a Chinese Case of B Cell Expansion With NF-κB and T Cell Anergy

2021 ◽  
Vol 12 ◽  
Author(s):  
Peiwei Zhao ◽  
Qingjie Meng ◽  
Yufeng Huang ◽  
Lei Zhang ◽  
Sukun Luo ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Expansion ◽  
Nk Cell ◽  
Cell Activity ◽  
Heterozygous Mutation ◽  
Sequencing Analysis ◽  
Nk Cell Activity ◽  
T Cell Anergy ◽  
Cell Anergy

B cell expansion with NF-κB and T cell anergy (BENTA) is a rare primary immunodeficiency disorder caused by gain-of-function (GOF) mutations in the CARD11 gene. Affected patients present with persistent B cell lymphocytosis in early childhood paired with lymphadenopathy and splenomegaly. Until now only six activating mutations from 14 patients have been reported in CARD11. Here we report a patient from China with polyclonal B cell lymphocytosis and frequent infections in early life. A heterozygous mutation (c.377G>A, G126D) in exon 5 of CARD11 gene (NM_032415) was identified by whole exome sequencing. In vitro functional studies showed that the G126D mutation is associated with increased expression of CARD11 and NF-κB activation in Hela cells. Flow cytometry analysis indicated NK cell activity and CD107a degranulation of the patient were decreased. RNA sequencing analysis showed that a number of genes in NF-κB pathway increased while those involved in NK cell activity and degranulation were down-regulated. In summary, our work identified a de novo germline GOF mutation in CARD11 with functional evidence of BENTA.

scholarly journals Intrinsic Plasma Cell Differentiation Defects in B Cell Expansion with NF-κB and T Cell Anergy Patient B Cells

2017 ◽  
Vol 8 ◽  
Author(s):  
Swadhinya Arjunaraja ◽  
Brent D. Nosé ◽  
Gauthaman Sukumar ◽  
Nathaniel M. Lott ◽  
Clifton L. Dalgard ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Plasma Cell ◽  
Cell Expansion ◽  
Plasma Cell Differentiation ◽  
T Cell Anergy ◽  
Cell Anergy

scholarly journals The First Case of BENTA Disease (B Cell Expansion with NF-κB and T Cell Anergy) from Iran

2021 ◽  
Author(s):  
Maryam Neishabury ◽  
Azita Azarkeivan ◽  
Maghsood Mehri ◽  
Hossein Najmabadi ◽  
Taher Cheraghi
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Expansion ◽  
T Cell Anergy ◽  
First Case ◽  
Cell Anergy

scholarly journals Clinical, Immunological, and Molecular Findings in Four Cases of B Cell Expansion With NF-κB and T Cell Anergy Disease for the First Time From India

2018 ◽  
Vol 9 ◽  
Author(s):  
Maya Gupta ◽  
Jahnavi Aluri ◽  
Mukesh Desai ◽  
Madhukar Lokeshwar ◽  
Prasad Taur ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Expansion ◽  
T Cell Anergy ◽  
Cell Anergy ◽  
First Time

scholarly journals A Novel, Heterozygous Three Base-Pair Deletion in CARD11 Results in B Cell Expansion with NF-κB and T Cell Anergy Disease

2020 ◽  
Vol 40 (2) ◽  
pp. 406-411
Author(s):  
Adrian M. Shields ◽  
Bradly M. Bauman ◽  
Chantal E. Hargreaves ◽  
Andrew J. Pollard ◽  
Andrew L. Snow ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Base Pair ◽  
Cell Expansion ◽  
T Cell Anergy ◽  
Base Pair Deletion ◽  
Cell Anergy

CD40-Activated B-Cell Chronic Lymphocytic Leukemia Cells for Tumor Immunotherapy: Stimulation of Allogeneic Versus Autologous T Cells Generates Different Types of Effector Cells

Blood ◽  
1999 ◽  
Vol 93 (6) ◽  
pp. 1992-2002 ◽  
Author(s):  
Raymund Buhmann ◽  
Annette Nolte ◽  
Doreen Westhaus ◽  
Bertold Emmerich ◽  
Michael Hallek
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Tumor Antigens ◽  
Lymphocytic Leukemia ◽  
T Cell Anergy ◽  
Cell Anergy ◽  
Cell Chronic Lymphocytic Leukemia ◽  
Stimulation Of

Although spontaneous remissions may rarely occur in B-cell chronic lymphocytic leukemia (B-CLL), T cells do generally not develop a clinically significant response against B-CLL cells. Because this T-cell anergy against B-CLL cells may be caused by the inability of B-CLL cells to present tumor-antigens efficiently, we examined the possibility of upregulating critical costimulatory (B7-1 and B7-2) and adhesion molecules (ICAM-1 and LFA-3) on B-CLL cells to improve antigen presentation. The stimulation of B-CLL cells via CD40 by culture on CD40L expressing feeder cells induced a strong upregulation of costimulatory and adhesion molecules and turned the B-CLL cells into efficient antigen-presenting cells (APCs). CD40-activated B-CLL (CD40-CLL) cells stimulated the proliferation of both CD4+ and CD8+ T cells. Interestingly, stimulation of allogeneic versus autologous T cells resulted in the expansion of different effector populations. Allogeneic CD40-CLL cells allowed for the expansion of specific CD8+cytolytic T cells (CTL). In marked contrast, autologous CD40-CLL cells did not induce a relevant CTL response, but rather stimulated a CD4+, Th1-like T-cell population that expressed high levels of CD40L and released interferon-γ in response to stimulation by CD40-CLL cells. Together, these results support the view that CD40 activation of B-CLL cells might reverse T-cell anergy against the neoplastic cell clone, although the character of the immune response depends on the major histocompatibility complex (MHC) background on which the CLL or tumor antigens are presented. These findings may have important implications for the design of cellular immunotherapies for B-CLL.

NK Cell Activity Influences Long Term Outcome of Pediatric Leucemias After T Cell Depleted Stem Cell Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4141-4141
Author(s):  
Peter Lang ◽  
Matthias Pfeiffer ◽  
Heiko-Manuel Teltschik ◽  
Paul G. Schlegel ◽  
Tobias F. Feuchtinger ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Relapse Rate ◽  
Nk Cell ◽  
Cell Activity ◽  
Nk Activity ◽  
Nk Cell Activity ◽  
Cell Recovery ◽  
Magnetic Microbeads

Abstract Abstract 4141 T cell depletion with magnetic microbeads can effectively reduce GvHD rates after stem cell transplantation from both mismatched related donors as well as from matched or partially matched unrelated donors. However, T cell recovery is markedly delayed after this procedure and T cell mediated antileukemic effects may be reduced. Thus, we focused on the rapidly regenerating donor derived NK cell system and addressed the question, whether its functional activity would influence the probability of relapse in a long term analysis. Temporal development of NK cell activity was monitored in 47 pediatric patients with leukemias (ALL, AML, CML, JMML) and myelodysplastic syndromes after transplantation of T cell depleted stem cells from matched unrelated (n=18) and mismatched related (haploidentical, n=29) donors with a median follow up of 7.4 years (2.1–12). 38 patients had CR1-3, 9 patients had active disease at time of transplantation. EFS and relapse rate at 5 years for the entire group were 36% and 40%, respectively (EFS and relapse rate for ALL patients in CR1-3: 50% and 36%; EFS and relapse rate for AML/MDS patients: 22% and 30%). CD34+ selection with magnetic microbeads resulted in 8×103/kg residual T cells. No posttransplant immune suppression was given. 89% of the patients had no GvHD, 9% had GvHD grade I and only 2 patients had GvHD grade II or III. NK cells recovered rapidly after transplantation (300 CD56+/μL at day 30, median), whereas T cell recovery was delayed (median: 12 CD3+/μL at day 90). NK activity was measured as specific lysis of K562 targets several times after transplantation (mean: 3 assays per patient). Four temporal patterns of lytic activity could be differentiated: consistently low, consistently high, decreasing and increasing activity. Patients with consistently high or increasing activity had significantly lower relapse probability than patients with consistently low or decreasing levels (0.18 vs 0.73 at 5 years, p<0.05). The subgroup of patients with ALL showed similar results (0.75 vs 0.14 at 5 years, p<0.05). Speed of T cell recovery had no influence. These data suggest that both achieving and maintaining a high level of NK activity may contribute to prevent relapse. Thus, this model comprises direct functional data in the form of NK cell activation levels which are likely to be influenced by the presence of different cytokines in each patient. Our observations may have some clinical implications: immunomagnetic depletion of T cells prevents GvHD and can be performed in pediatric leukemias in remission without excessive increase in relapse rates. High levels of NK activity seem to be of importance. Since NK activity could be markedly increased by in vitro stimulation with Interleukin 2 (IL-2), in vivo administration should be considered. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Comparative effects of six probiotic strains on immune functionin vitro

2011 ◽  
Vol 108 (3) ◽  
pp. 459-470 ◽  
Author(s):  
Honglin Dong ◽  
Ian Rowland ◽  
Parveen Yaqoob
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
Nk Cell ◽  
Bifidobacterium Longum ◽  
Cell Activity ◽  
T Cell Subsets ◽  
Nk Cell Activity ◽  
Tnf Α ◽  
Significant Difference ◽  
Probiotic Strains

There is considerable interest in the strain specificity of immune modulation by probiotics. The present study compared the immunomodulatory properties of six probiotic strains of different species and two genera in a human peripheral blood mononuclear cell (PBMC) modelin vitro. Live cells of lactobacilli (Lactobacillus caseiShirota,L. rhamnosusGG,L. plantarumNCIMB 8826 andL. reuteriNCIMB 11951) and bifidobacteria (Bifidobacterium longumSP 07/3 andB. bifidumMF 20/5) were individually incubated with PBMC from seven healthy subjects for 24 h. Probiotic strains increased the proportion of CD69+on lymphocytes, T cells, T cell subsets and natural killer (NK) cells, and increased the proportion of CD25+, mainly on lymphocytes and NK cells. The effects on activation marker expression did not appear to be strain specific. NK cell activity was significantly increased by all six strains, without any significant difference between strains. Probiotic strains increased production of IL-1β, IL-6, IL-10, TNF-α, granulocyte-macrophage colony-stimulating factor and macrophage inflammatory protein 1α to different extents, but had no effect on the production of IL-2, IL-4, IL-5 or TNF-β. The cytokines that showed strain-specific modulation included IL-10, interferon-γ, TNF-α, IL-12p70, IL-6 and monocyte chemotactic protein-1. TheLactobacillusstrains tended to promote T helper 1 cytokines, whereas bifidobacterial strains tended to produce a more anti-inflammatory profile. The results suggest that there was limited evidence of strain-specific effects of probiotics with respect to T cell and NK cell activation or NK cell activity, whereas production of some cytokines was differentially influenced by probiotic strains.

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