Human B cells infected by Trypanosoma cruzi undergo F-actin disruption and cell death via caspase-7 activation and cleavage of phospholipase Cγ1

Immunobiology ◽  
2020 ◽  
Vol 225 (3) ◽  
pp. 151904 ◽  
Author(s):  
Marlus Alves dos Santos ◽  
Flávia Alves Martins ◽  
Bruna Cristina Borges ◽  
Júlia de Gouveia Santos ◽  
Rosiane Nascimento Alves ◽  
...  
Keyword(s):  
Cell Death ◽  
B Cells ◽  
Trypanosoma Cruzi ◽  
Human B Cells ◽  
Phospholipase Cγ1 ◽  
Caspase 7

scholarly journals Rotavirus Differentially Infects and Polyclonally Stimulates Human B Cells Depending on Their Differentiation State and Tissue of Origin

2010 ◽  
Vol 84 (9) ◽  
pp. 4543-4555 ◽  
Author(s):  
Carlos F. Narváez ◽  
Manuel A. Franco ◽  
Juana Angel ◽  
John M. Morton ◽  
Harry B. Greenberg
Keyword(s):  
Cell Death ◽  
B Cells ◽  
Viral Replication ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Human B Cells ◽  
Tissue Of Origin ◽  
Differentiation Stage

ABSTRACT We have shown previously that rotavirus (RV) can infect murine intestinal B220+ cells in vivo (M. Fenaux, M. A. Cuadras, N. Feng, M. Jaimes, and H. B. Greenberg, J. Virol. 80:5219-5232, 2006) and human blood B cells in vitro (M. C. Mesa, L. S. Rodriguez, M. A. Franco, and J. Angel, Virology 366:174-184, 2007). However, the effect of RV on B cells, especially those present in the human intestine, the primary site of RV infection, is unknown. Here, we compared the effects of the in vitro RV infection of human circulating (CBC) and intestinal B cells (IBC). RV infected four times more IBC than CBC, and in both types of B cells the viral replication was highly restricted to the memory subset. RV induced cell death in 30 and 3% of infected CBC and IBC, respectively. Moreover, RV induced activation and differentiation into antibody-secreting cells (ASC) of CBC but not IBC when the B cells were present with other mononuclear cells. However, RV did not induce these effects in purified CBC or IBC, suggesting the participation of other cells in activating and differentiating CBC. RV infection was associated with enhanced interleukin-6 (IL-6) production by CBC independent of viral replication. The infection of the anti-B-cell receptor, lipopolysaccharide, or CpG-stimulated CBC reduced the secretion of IL-6 and IL-8 and decreased the number of ASC. These inhibitory effects were associated with an increase in viral replication and cell death and were observed in polyclonally stimulated CBC but not in IBC. Thus, RV differentially interacts with primary human B cells depending on their tissue of origin and differentiation stage, and it affects their capacity to modulate the local and systemic immune responses.

scholarly journals Manganese induces apoptosis of human B cells: caspase-dependent cell death blocked by Bcl-2

1999 ◽  
Vol 6 (5) ◽  
pp. 445-453 ◽  
Author(s):  
Nicolas Schrantz ◽  
Dominique A Blanchard ◽  
Françoise Mitenne ◽  
Marie-Thérèse Auffredou ◽  
Aimé Vazquez ◽  
...  
Keyword(s):  
Cell Death ◽  
B Cells ◽  
Human B Cells ◽  
Dependent Cell

scholarly journals Neisseria gonorrhoeae Kills Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 (CD66a)-Expressing Human B Cells and Inhibits Antibody Production

2005 ◽  
Vol 73 (7) ◽  
pp. 4171-4179 ◽  
Author(s):  
Milica Pantelic ◽  
Young-June Kim ◽  
Silvia Bolland ◽  
Ines Chen ◽  
John Shively ◽  
...  
Keyword(s):  
Cell Death ◽  
B Cells ◽  
Neisseria Gonorrhoeae ◽  
Carcinoembryonic Antigen ◽  
Adhesion Molecule ◽  
Antibody Production ◽  
Cellular Adhesion ◽  
Cell Death Pathway ◽  
Human B Cells ◽  
Cellular Adhesion Molecule

ABSTRACT Neisseria gonorrhoeae cells (gonococci [GC]), the etiological agents for gonorrhea, can cause repeated infections. During and after gonococcal infection, local and systemic antigonococcal antibody levels are low. These clinical data indicate the possibility that GC may suppress immune responses during infection. Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1 or CD66a), a receptor for GC opacity (Opa) proteins, was shown to mediate inhibitory signals. In the present study, human B cells were activated by interleukin-2 to express CEACAM1 and then stimulated to secrete antibodies and simultaneously coincubated with Opa− and OpaI GC of strain MS11. Our results show that this OpaI GC has the ability to inhibit antibody production. The interaction of GC and CEACAM1 with human peripheral B cells also results in induction of cell death. The same findings were observed in DT40 B cells. This CEACAM1-promoted cell death pathway does not involve the inhibitory signals or the tyrosine phosphatases SHP-1 and SHP-2 but depends on Bruton's tyrosine kinase in DT40 cells. Our results suggest that Neisseria gonorrhoeae possesses the ability to suppress antibody production by killing CEACAM1-expressing B cells.

scholarly journals Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death.

1993 ◽  
Vol 90 (18) ◽  
pp. 8479-8483 ◽  
Author(s):  
S. Henderson ◽  
D. Huen ◽  
M. Rowe ◽  
C. Dawson ◽  
G. Johnson ◽  
...  
Keyword(s):  
Cell Death ◽  
B Cells ◽  
Programmed Cell Death ◽  
Epstein Barr Virus ◽  
Protein A ◽  
Barr Virus ◽  
Human B Cells ◽  
Epstein Barr

Bone Morphogenetic Proteins Inhibit CD40L- and IL-21-Induced Ig Production In Human B Cells: Differential Effects of BMP-6 and BMP-7

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1745-1745
Author(s):  
Kanutte Huse ◽  
Maren Bakkeb∅ ◽  
Lise Forfang ◽  
Vera I. Hilden ◽  
Erlend B. Smeland ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcription Factors ◽  
B Cells ◽  
B Cell ◽  
Plasma Cell ◽  
Bone Morphogenetic Proteins ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Memory B Cells ◽  
Human B Cells

Abstract Abstract 1745 Introduction: TGF-β has been shown to play an important role in directing class switch recombination in human B cells. Bone morphogenetic proteins (BMPs) are members of the TGF-β family, and we have previously shown that BMP-6 inhibits proliferation of B cell progenitors as well as mature B cells in humans. However, how various BMP members affect Ig production and B-cell maturation to plasma cells have not been investigated. Here we studied the effects of various BMPs in CD27- naive and CD27+ memory B cells from peripheral blood of healthy human donors. Methods: We used flow immunomagnetic beads and flow cytometry cell sorting to purify CD19+CD27- naive and CD19+CD27+ memory B cells from peripheral blood of healthy donors, and investigated BMP induced effects on in vitro proliferation, cell death and Ig production as measured by thymidine incorporation assay, propidium iodide staining and ELISA, respectively. To separate direct inhibition of plasma cell differentiation from indirect effects via suppression of proliferation and induction of apoptosis, CFSE tracking of cell division was combined with immunophenotyping of cultured cells to identify CD27+CD38+ plasma cells. Expression of transcription factors and AICDA were measured by quantitative real-time PCR. Results: BMP-2, -4, -6 and -7 specifically inhibited CD40L- and IL-21-induced production of IgM, IgG and IgA. BMP-6 was the most potent inhibitor, reducing the Ig production by 70% in memory B cells and more than 50% in naive B cells. By investigating the mechanisms for reduced Ig production, we found a striking difference between the structurally similar BMP-6 and BMP-7. BMP-6 directly inhibited differentiation to CD27+CD38+ plasma cells, whereas BMP-7 only had minor effects on differentiation. Instead, BMP-7 mainly affected Ig production indirectly by inducing apoptosis. Furthermore, we explored BMP-6-induced signaling and gene regulation in more detail in memory B cells. BMP-6 up-regulated Id1, Id2 and Id3 gene expression in CD40L- and IL-21-stimulated cells (6.1-fold, 1.7-fold and 4.0-fold induction after 48 hours culture with BMP-6, respectively). In contrast, BMP-6 potently inhibited CD40L- and IL-21-induced upregulation of the transcription factor XBP-1, necessary for the late stages of plasmacytic differentiation. Expression of transcription factors regulating earlier stages (IRF4, PRDM1) was not affected, indicating that BMP-6 only modulates late events of plasma cell development. Conclusion: These results show that BMPs potently suppress Ig production in mature human B cells by inhibiting differentiation or by inducing cell death. Disclosures: No relevant conflicts of interest to declare.

Heparin induces amyloid formation in cultured human isletss

2007 ◽  
Vol 30 (4) ◽  
pp. 92 ◽  
Author(s):  
K Potter ◽  
K Park
Keyword(s):  
Cell Death ◽  
B Cells ◽  
Islet Transplantation ◽  
Islet Cell ◽  
Human Islets ◽  
Fibril Formation ◽  
Amyloid Formation ◽  
Secretory Product ◽  
Islet Amyloid ◽  
Heparin Sulfate

Background: Pancreatic islet transplantation offers improved glycemic control in type 1 diabetic patients above standard insulin therapy, ideally minimizing macro- and microvascular complications of diabetes mellitus. However success is limited thus far, with fewer than 10% of patients retaining insulin independence at two years post-transplantation. In addition to immune rejection, many non-immune factors may promote long-term graft secretory dysfunction and loss of viable graft mass. One such important non-immune factor may be the formation of islet amyloid, a pathologic lesion of the islet in type 2 diabetes that contributes to the progressive loss of b cells in that disease and that has been shown to form rapidly in human islets transplanted into NOD.scid mice. Amyloid deposits are composed primarily of the b cell secretory product islet amyloid polypeptide (IAPP), are cytotoxic, and develop in environments in which b cells are stressed. Heparin sulfate is used as an anti-coagulant in clinical islet transplantation and to prevent the instant blood-mediated inflammatory reaction (IBMIR), which occurs upon contact between islets and blood and may destroy a substantial proportion of the grafted islet mass. However, heparin is also known to stimulate amyloid fibril formation. Methods: To determine whether heparin may enhance amyloid formation in human islets and contribute to graft failure, we cultured isolated human islets in the presence or absence of heparin sulfate (42 and 420 units/ml) for 2 weeks in 11.1 mM glucose. Results: Histological assessment of sections of cultured islets for the presence of amyloid (by thioflavin S staining) revealed a marked, concentration-dependent increase in amyloid deposition following culture in the presence of heparin. Quantitative analysis of these sections showed that the proportion of islet area comprised of amyloid was increased approximately 2-fold (0.15%±0.12% vs 0.46%±0.15% of islet area) following culture in 42 units/ml heparin, and the proportion of islets in which amyloid was detectable (amyloid prevalence) was also increased (35%±24% vs 68%±10% of islets). At 420 units/ml heparin, the amyloid area was even greater (0.23%±0.15% vs 0.97%±0.42% of islet area) as was the amyloid prevalence (53%±29% vs 81%±14% of islets). To affirm that heparin can stimulate IAPP fibrillogenesis and enhance IAPP toxicity, we incubated synthetic human IAPP in the presence of heparin and measured amyloid formation in real time by thioflavin T fluorescence, and cell toxicity by Alamar blue viability assay in transformed rat (INS-1) ß-cell cultures. Heparin stimulated IAPP fibril formation and increased death of INS-1 cells exposed to IAPP (78.2%±10.9% vs 51.8%±12.2% of control viability), suggesting that heparin stimulates IAPP aggregation and toxicity. Remarkably, preliminary assessment of human islets cultured in heparin did not show increased islet cell death by TUNEL staining or loss of insulin immunostaining. Conclusion: In summary, heparin increases amyloid formation in cultured human islets. Although our preliminary data does not suggest that heparin-induced amyloid formation contributes to islet cell death, we speculate that heparin-induced amyloid formation may contribute to graft dysfunction and that caution should be used in the clinical application of this drug in islet transplantation.

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