scholarly journals Altered frequency of CD24highCD38high transitional B cells in patients with cardiac involvement of chronic Chagas disease

2019 ◽  
Author(s):  
Magalí C. Girard ◽  
Gonzalo R. Acevedo ◽  
Micaela S. Ossowski ◽  
Paula B. Alcaráz ◽  
Marisa Fernández ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Chagas Disease ◽  
Peripheral Blood ◽  
Cardiac Involvement ◽  
Mononuclear Cells ◽  
Regulatory Function ◽  
Chronic Patients ◽  
B10 Cells ◽  
Chronic Chagas Disease

ABSTRACTThe cardiomyopathy developed by patients with chronic Chagas disease (CCD), one of the most severe consequences of T. cruzi infection, is mainly associated with an imbalance between an excessive inflammatory reaction and a defective immunomodulatory profile cause by host-parasite interaction. Despite the growing importance of the regulatory function of B-cells in many malignancies, few studies have addressed their immunosuppressive role in chronic Chagas disease. In this work, we tackled this issue by studying the proportion of different B cell subpopulations and their capacity to secrete IL-10 in individuals with distinct clinical forms of CCD. Seven-colour flow cytometry was performed to examine the peripheral blood B cell compartment in chronic Chagas disease (CCD) patients with and without cardiac manifestations (n=10 for each group) and non-infected donors (n=9). Peripheral blood mononuclear cells (PBMC) were incubated for 5h with PMA, ionomicyn and brefeldin A. According to the expression of markers CD19, CD24 and CD38, we showed an expansion of total B cell and transitional CD24highCD38high B cell subsets in CCD patients with cardiac involvement compared to non-infected donors. Furthermore, although no differences were observed in the frequency of total IL-10 producing B cells (B10) among the groups, CCD patients with cardiac involvement showed a statistically significant increased proportion of naïve B10 cells and a tendency to an increased frequency of transitional B10 cells compared to non-infected donors. These findings suggest that immature transitional CD24highCD38high B cells are greatly expanded in patients with the cardiac form of chronic Chagas disease and these cells retain their ability to secrete IL-10 compared to non-infected donors. Furthermore, the distribution of naïve, transitional and memory B cells inside the B10 cells followed the same pattern in chronic patients without cardiac involvement and non-infected individuals. Our work provides insight into the phenotypic distribution of regulatory B cell in CCD, an important step towards new strategies to prevent cardiomiopathy associated with T. cruzi infection.

scholarly journals Ex vivo characterization of Breg cells in patients with chronic Chagas disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Magalí C. Girard ◽  
Gonzalo R. Acevedo ◽  
Micaela S. Ossowski ◽  
Marisa Fernández ◽  
Yolanda Hernández ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Chagas Disease ◽  
Peripheral Blood ◽  
Cardiac Involvement ◽  
Ex Vivo ◽  
Regulatory Function ◽  
B Cell Subsets ◽  
B10 Cells ◽  
Chronic Chagas Disease

AbstractDespite the growing importance of the regulatory function of B cells in many infectious diseases, their immunosuppressive role remains elusive in chronic Chagas disease (CCD). Here, we studied the proportion of different B cell subsets and their capacity to secrete IL-10 ex vivo in peripheral blood from patients with or without CCD cardiomyopathy. First, we immunophenotyped peripheral blood mononuclear cells from patients according to the expression of markers CD19, CD24, CD38 and CD27 and we showed an expansion of total B cell and transitional CD24highCD38high B cell subsets in CCD patients with cardiac involvement compared to non-infected donors. Although no differences were observed in the frequency of total IL-10 producing B cells (B10) among the groups, CCD patients with cardiac involvement showed an increased proportion of naïve B10 cells and a tendency to a higher frequency of transitional B10 cells compared to non-infected donors. Our research demonstrates that transitional B cells are greatly expanded in patients with the cardiac form of CCD and these cells retain the ability to secrete IL-10. These findings provide insight into the phenotypic distribution of regulatory B cells in CCD, an important step towards new strategies to prevent cardiomyopathy associated with T. cruzi infection.

scholarly journals Trypanosoma cruzi Induces Regulatory B Cell Alterations in Patients With Chronic Chagas Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Magalí C. Girard ◽  
Micaela S. Ossowski ◽  
Arturo Muñoz-Calderón ◽  
Marisa Fernández ◽  
Yolanda Hernández-Vásquez ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Chagas Disease ◽  
Ex Vivo ◽  
Production Capacity ◽  
Cell Phenotype ◽  
Regulatory B Cell ◽  
B10 Cells ◽  
Chronic Chagas Disease

The clinical evolution of patients with chronic Chagas disease (CCD) is mainly associated with an excessive inflammation and a defective immunomodulatory profile caused by the interaction between T. cruzi and the host. Regulatory B (Breg) cells exert immune suppression mostly through IL-10 production (B10 cells), but also through IL-10-independent mechanisms. Previously, we demonstrated that CCD patients with cardiomyopathy show changes in the ex vivo Breg cell phenotypic distribution although maintain IL-10 production capacity. Here, we sought to identify potential alterations on Breg cells upon in vitro stimulation. Isolated B cells from CCD patients with or without cardiomyopathy and non-infected (NI) donors were stimulated with T. cruzi lysate or CpG + CD40L, and characterized by flow cytometry based on the expression of CD24, CD27, CD38, and the regulatory molecules IL-10 and PD-L1. IL-10 and IL-17 secretion in the supernatant of B cells was evaluated by ELISA. Data showed that T. cruzi stimulation diminished the expression of CD24 and CD38 on CD27− B cells while reducing the percentage of CD24high inside CD27+ B cells. Furthermore, T. cruzi induced a regulatory B cell phenotype by increasing B10 cells and IL-10 secretion in all the groups. The innate-like B10 cells expansion observed in patients with cardiomyopathy would be associated with CD27− B10 cell subsets, while no predominant phenotype was found in the other groups. Patients with cardiomyopathy also displayed higher IL-17 secretion levels in T. cruzi–activated B cells. CpG + CD40L stimulation revealed that B cells from CCD patients and NI donors had the same ability to differentiate into B10 cells and secrete IL-10 in vitro. Additionally, CCD patients showed an increased frequency of CD24−CD27− B cells and a reduction in the percentage of CD24highCD27+ Breg cells, which appeared to be inversely correlated with the presence of T. cruzi DNA in blood. Finally, CCD patients exhibited a higher frequency of PD-L1+ B cells in T. cruzi–stimulated samples, suggesting that IL-10-independent mechanisms could also be tangled in the control of inflammation. Altogether, our results provide evidence about the potential role of Breg cells in the immune response developed against T. cruzi and its contribution to chronic Chagas cardiomyopathy.

scholarly journals Changes of Regulatory T and B Cells in Patients with Papillary Thyroid Carcinoma after131I Radioablation: A Preliminary Study

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Lei Jiang ◽  
Yanxia Zhan ◽  
Yusen Gu ◽  
Yi Ye ◽  
Yunfeng Cheng ◽  
...  
Keyword(s):  
B Cells ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
B Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Papillary Thyroid ◽  
T And B Cells ◽  
Significant Difference ◽  
And Control

Introduction. Lymphocytic infiltration and specific lymphocytes subsets may play important roles in papillary thyroid carcinoma (PTC) progression and prognosis. In this study, we try to understand the influence of131I radioablation on the important lymphocytes subtypes of regulatory T and B cells (Tregs and Bregs).Methods. Peripheral blood mononuclear cells from 30 PTC patients before and after131I therapy, and 20 healthy donors were collected. The expression of Tregs (CD4+CD25+CD127-/low) and B cell (CD5+CD19+) and production and secretion of interleukin 10 (IL-10) were analyzed by FACS and ELISA assay, respectively.Results. For Tregs percentage in peripheral blood lymphocytes, there was no difference between pretreatment and control and between posttreatment and control. Compared with pretherapy, increased Tregs infiltration was noted in posttherapy (P<0.05). Although no difference was between pretreatment and control, compared with these two groups, decreased CD19+and CD5+CD19+B cell percentage in posttreatment was observed (P<0.05). Among these groups, no significant difference was displayed in intracellular IL-10 production and extracellular IL-10 secretion.Conclusions.131I Radioablation increased Tregs and decreased CD19+and CD5+CD19+B cells percentage after treatment. However, it has no effect on IL-10 and lymphocytes in peripheral blood. Therefore, longer follow-up of Tregs and Bregs should be further investigated.

Interleukin 21-Based Therapy Can Induce Human B Cells To Produce Granzyme B and Express Other Features of Cytotoxic Lymphocytes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3886-3886
Author(s):  
Bernd Jahrsdoerfer ◽  
Sue M. Blackwell ◽  
George J. Weiner
Keyword(s):  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
De Novo ◽  
Granzyme B ◽  
Brefeldin A ◽  
Peripheral Blood Mononuclear ◽  
Human B Cells ◽  
Interleukin 21

Abstract B cells are not currently known to be capable of producing granzyme B or being cytotoxic. We recently found that human B cells activated with Interleukin 21 (IL-21) and antibodies to the B cell receptor (BCR) or immunostimulatory oligonucleotides (CpG ODN), can produce granzyme B. Further studies were done to assess the biological and potential therapeutic significance of this finding. Granzyme B ELISpot, intracellular staining for granzyme-B, quantitative real time RT-PCR for granzyme B messenger RNA and gene expression array confirmed B cells obtained from the peripheral blood of normal individuals (Fig. 1) and many B cell lines including Namalwa, Daudi, Ramos and EBV-transformed lymphoblasts, can be induced to produce granzyme B. This granzyme B is functional as demonstrated by cleavage of a granzyme B-sensitive colorimetric substrate. IL-21 based treatment also increased the transcription of the gene for perforin and the production of Interferon-γ in select B cell populations. We conclude that IL-21 based therapy can induce B cells to produce functional granzyme B and other components known to be present in the cytotoxic granules of CTL and NK cells. These unexpected findings could have significant implications on our understanding of the role of B cells in immune regulation and for a variety of immune phenomena including auto-, cancer and infectious immunity. Figure 1. Interleukin 21 (IL-21) induces de-novo synthesis of Granzyme B by activated B cells. Peripheral blood mononuclear cells (PBMC) were stimulated with the above depicted agents for 18 hours. After further incubtion with Brefeldin A for 4 hours cells were harvested, fixed, permeabilized, stained with PE- and PE-Cy5-labeled antibodies against Granzyme B and CD19, and analyzed flowcytometrically. Figure 1. Interleukin 21 (IL-21) induces de-novo synthesis of Granzyme B by activated B cells. Peripheral blood mononuclear cells (PBMC) were stimulated with the above depicted agents for 18 hours. After further incubtion with Brefeldin A for 4 hours cells were harvested, fixed, permeabilized, stained with PE- and PE-Cy5-labeled antibodies against Granzyme B and CD19, and analyzed flowcytometrically.

scholarly journals OP0024 DECREASED LEVELS OF T FOLLICULAR HELPER (CD4+CXCR5+) CELLS AND CD27+CD38+ AND CD27+CD38- B CELLS IN ANKYLOSING SPONDYLITIS PATIENTS CORRELATE WITH MARKER OF INFLAMMATION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 13.2-14
Author(s):  
H. Forsblad-D’elia ◽  
U. Hellman ◽  
A. Kumar ◽  
K. Lejon
Keyword(s):  
Ankylosing Spondylitis ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Female Patients ◽  
Tfh Cells ◽  
Follicular Helper ◽  
B Cell Subsets

Background:The role of different lymphocyte subsets in ankylosing spondylitis (AS) is still to be elucidated. It has previously been reported contradictory data concerning the levels of T Follicular Helper (TFH) cells and differentiated B cells in peripheral blood of AS patients. In addition, the connection to disease related parameters is still to be fully revealed.Objectives:The purpose of this study was to investigate the level of CD4+TFH cells and CD27+CD38+/CD38- B cells in patients with AS from northern Sweden and to compare the levels with age and sex-matched controls. We also studied associations between these cell subsets and disease related factors.Methods:Peripheral blood mononuclear cells (PBMSc) from a cohort of 50 patients with AS from Region Västerbotten (mean age 52±9.1 years, 33 (66 %) men, 50 (100 %) HLAB27 positive) and 50 pair wise matched blood donor controls (mean age 54±8.8 years, 33 (66 %) men) were stained with a combination of antibodies allowing for the detection of CD27, CD38, CD19, CD3, CD4 and CXCR5 markers and analyzed by flow cytometry. In addition, the patient with AS were examined with spinal x-ray for radiographic alterations assessed with mSASSS. CRP and ESR were measured and physical function and disease activity were registered with BASMI and BASFI respectively ASDAS-CRP and BASDAI.Results:When comparing AS patients and controls pair wise, we observed on average a 50% reduction of TFH (CD3+CD4+CXCR5+) cells among CD45+ lymphocytes in PBMCs from patients (p=0,000008). Furthermore, a 20-30% reduction among memory/plasma cells (CD19+CD27+CD38+ and CD19+CD27+CD38-) among CD45+ lymphocytes in PBMCs from patients (p=0,002 and p=0,007 respectively). For female patients a correlation between TFH and ESR (Rs=-0,551 p=0,022) was observed. Moreover, negative correlations between the two B cell subsets (CD19+CD27+CD38+ and CD19+CD27+CD38-) and ESR were observed for female patients (Rs =–0,476 p=0,053 and Rs =–0,522 p=0,032 respectively).Conclusion:TFH cells was reduced in AS patients and this reduction correlated with a reduction in differentiated (CD27+CD38+ and CD27+CD38-) B cells. In addition, the inflammation marker ESR was negatively correlated with TFH as well as with the differentiated B cell subsets in female patients. Our observations indicates a role of the humoral immune response in AS.Disclosure of Interests:None declared

scholarly journals Changes in Proteome Profile of Peripheral Blood Mononuclear Cells in Chronic Chagas Disease

2016 ◽  
Vol 10 (2) ◽  
pp. e0004490 ◽  
Author(s):  
Nisha Jain Garg ◽  
Kizhake V. Soman ◽  
Maria P. Zago ◽  
Sue-Jie Koo ◽  
Heidi Spratt ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Proteome Profile ◽  
Chronic Chagas Disease

scholarly journals B220 expression as an immunological marker for differentiation of Feline Leukemia Virus carrying cats

2020 ◽  
Vol 50 (12) ◽  
Author(s):  
Isadora Duarte Santos Frota ◽  
Jéssica de Oliveira Souza ◽  
Fernanda de Oliveira Busato ◽  
Cristina Abreu de Araujo ◽  
Flávio Curbani ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Feline Immunodeficiency Virus ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Viral Infections ◽  
Leukemia Virus ◽  
Clinical Signs ◽  
Feline Leukemia Virus ◽  
Immunodeficiency Virus

ABSTRACT: Feline leukemia virus (FeLV) causes an infection in cats that, in some cases, can also be reported with other pathologies, such as infection with feline immunodeficiency virus (FIV), feline infectious peritonitis (FIP), and lymphoma. Although, a compromised immune response is reported in these animals, little is known about the immunological state of their cells. To shed some light in this area, we studied peripheral blood samples from both infected and non-infected cats with FeLV, with or without FIV, FIP, and lymphoma. We tested a panel of monoclonal antibodies (n=11) against mouse and human antigens and we reported that cat leukocytes can be stained with anti-mouse B220 monoclonal antibody; therefore, percentages of B cells were evaluated in different cat groups. Our results showed that cats with FeLV and FIP, or with leukemia, presented a large decrease in B220+ mononuclear cells. However, FeLV+ cats without clinical signs, or with unspecific clinical signs, had the same amount of B220+ mononuclear cells as healthy cats (control cats). Since the expression of B220 is exclusively restricted to the naïve B cell population, we inferred that the absence of these B cells in FeLV+ cats is related to other conditions that affect B cell numbers, such as viral infections and leukemias. Therefore, the amount of naïve B cells in peripheral blood (i.e., B220+ cells) can be used to identify FeLV+ cats concomitantly carrying FIP or leukemia, from FeLV+ cats with lymphoma or without any clinical signs.

scholarly journals Abnormal B-Cell and Tfh-Cell Profiles in Patients With Parkinson Disease

2021 ◽  
Vol 9 (2) ◽  
pp. e1125
Author(s):  
Rui Li ◽  
Thomas Francis Tropea ◽  
Laura Rosa Baratta ◽  
Leah Zuroff ◽  
Maria E. Diaz-Ortiz ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Parkinson Disease ◽  
B Cell ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Ex Vivo ◽  
Cell Counts

Background and ObjectivesThere has been growing interest in potential roles of the immune system in the pathogenesis of Parkinson disease (PD). The aim of the current study was to comprehensively characterize phenotypic and functional profiles of circulating immune cells in patients with PD vs controls.MethodsPeripheral blood was collected from patients with PD and age- and sex-matched neurologically normal controls (NCs) in 2 independent cohorts (discovery and validation). Comprehensive multicolor flow cytometry was performed on whole blood leukocytes and peripheral blood mononuclear cells to characterize different immune subsets and their ex vivo responses.ResultsThe discovery cohort included 17 NCs and 12 participants with PD, and the validation cohort included 18 NCs and 18 participants with PD. Among major immune cell types, B cells appeared to be preferentially affected in PD. Proliferating B cell counts were decreased in patients with PD compared with controls. Proportions of B-cell subsets with regulatory capacity such as transitional B cells were preferentially reduced in the patients with PD, whereas proportions of proinflammatory cytokine-producing B cells increased, resulting in a proinflammatory shift of their B-cell functional cytokine responses. Unsupervised principal component analysis revealed increased expression of TNFα and GM-CSF by both B cells and T cells of patients with PD. In addition, levels of follicular T cells, an important B-cell helper T-cell population, decreased in the patients with PD, correlating with their B-cell abnormality.DiscussionOur findings define a novel signature of peripheral immune cells and implicate aberrant Tfh:B-cell interactions in patients with PD.

scholarly journals Lupus Nephritis Correlates with B-Cell Interferon-β, Anti-Smith, and Anti-DNA: A Retrospective Study

2021 ◽  
Author(s):  
Fatima Alduraibi ◽  
Huma Fatima ◽  
Jennie Hamilton ◽  
W.Winn Chatham ◽  
Hui-Chen Hsu ◽  
...  
Keyword(s):  
B Cells ◽  
Lupus Nephritis ◽  
Basement Membrane ◽  
B Cell ◽  
Glomerular Basement Membrane ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interferon Β ◽  
Histopathological Features ◽  
Glomerular Lesions

Abstract Background: In systemic lupus erythematosus (SLE), detection of interferon-β (IFNβ)in B cells was found to be most prominent in patients with high anti-Smith (Sm) and renal disease, but a mechanistic connection was not clear. The objective of the present study is to determine the association of IFNβ in peripheral blood naïve B cells with the histopathological features of lupus nephritis (LN).Methods: The percentage of IFNβ+ cells in IgD+CD27− naïve CD19+ B cells (B-cell IFNβ) among peripheral blood mononuclear cells (PBMCs) from 80 SLE patients were analyzed using flow cytometry. Serological and clinical data were collected. The correlations of B-cell IFNβ with LN classification and with histopathological findings (light, electron and immunofluorescence [IF] microscopic analyses for deposition of IgM, IgG, IgA, C1q, and C3) were determined in 23 available biopsy specimens.Results: B-cell IFNβ is positively associated with anti-Sm (p = 0.001), anti-DNA (p = 0.010), and LN (p = 0.001), but was negatively associated with oral/nasal ulcer (p = 0.003) and photosensitivity (p = 0.045). B-cell IFNβ positively correlated with immune complex (IC) deposit in the glomerular basement membrane (GBM) (p = 0.002) but not in the mesangial (p = 0.107) or tubular region (p = 0.313). Patients with high B-cell IFNβ had statistically increased development of the proliferative LN (Classes III, IV and/or V), compared to patients with low B-cell IFNβ (p < 0.0001). Histopathological features positively associated with increased B-cell IFNβ included active glomerular lesions as determined by fibrocellular crescents (p = 0.023), chronic glomerular lesions indicated by segmental sclerosis (p = 0.033), and a membranous pattern of renal damage indicated by spike/holes (p = 0.015).Conclusion: B-cell IFNβ correlates with severe LN, glomerular basement membrane (GBM) IC deposition, and anatomical features of both active and chronic glomerular lesions.

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