scholarly journals Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells

Blood ◽  
2007 ◽  
Vol 110 (12) ◽  
pp. 3978-3984 ◽  
Author(s):  
Silke F. Fischer ◽  
Philippe Bouillet ◽  
Kristy O'Donnell ◽  
Amanda Light ◽  
David M. Tarlinton ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
B Cells ◽  
Cell Types ◽  
Memory B Cells ◽  
Death Process ◽  
Programmed Death ◽  
Cell Death Process ◽  
A Cell ◽  
First Time

Abstract T cell–dependent B-cell immune responses induce germinal centers that are sites for expansion, diversification, and selection of antigen-specific B cells. During the immune response, antigen-specific B cells are removed in a process that favors the retention of cells with improved affinity for antigen, a cell death process inhibited by excess Bcl-2. In this study, we examined the role of the BH3-only protein Bim, an initiator of apoptosis in the Bcl-2–regulated pathway, in the programmed cell death accompanying an immune response. After immunization, Bim-deficient mice showed persistence of both memory B cells lacking affinity-enhancing mutations in their immunoglobulin genes and antibody-forming cells secreting low-affinity antibodies. This was accompanied by enhanced survival of both cell types in culture. We have identified for the first time the physiologic mechanisms for killing low-affinity antibody-expressing B cells in an immune response and have shown this to be dependent on the BH3-only protein Bim.

scholarly journals Ions, the Movement of Water and the Apoptotic Volume Decrease

2020 ◽  
Vol 8 ◽  
Author(s):  
Carl D. Bortner ◽  
John A. Cidlowski
Keyword(s):  
Cell Death ◽  
Cell Volume ◽  
Cell Types ◽  
Regulatory Mechanisms ◽  
Death Process ◽  
Cell Shrinkage ◽  
Apoptotic Volume Decrease ◽  
Cell Death Process ◽  
A Cell ◽  
Volume Decrease

The movement of water across the cell membrane is a natural biological process that occurs during growth, cell division, and cell death. Many cells are known to regulate changes in their cell volume through inherent compensatory regulatory mechanisms. Cells can sense an increase or decrease in their cell volume, and compensate through mechanisms known as a regulatory volume increase (RVI) or decrease (RVD) response, respectively. The transport of sodium, potassium along with other ions and osmolytes allows the movement of water in and out of the cell. These compensatory volume regulatory mechanisms maintain a cell at near constant volume. A hallmark of the physiological cell death process known as apoptosis is the loss of cell volume or cell shrinkage. This loss of cell volume is in stark contrast to what occurs during the accidental cell death process known as necrosis. During necrosis, cells swell or gain water, eventually resulting in cell lysis. Thus, whether a cell gains or loses water after injury is a defining feature of the specific mode of cell death. Cell shrinkage or the loss of cell volume during apoptosis has been termed apoptotic volume decrease or AVD. Over the years, this distinguishing feature of apoptosis has been largely ignored and thought to be a passive occurrence or simply a consequence of the cell death process. However, studies on AVD have defined an underlying movement of ions that result in not only the loss of cell volume, but also the activation and execution of the apoptotic process. This review explores the role ions play in controlling not only the movement of water, but the regulation of apoptosis. We will focus on what is known about specific ion channels and transporters identified to be involved in AVD, and how the movement of ions and water change the intracellular environment leading to stages of cell shrinkage and associated apoptotic characteristics. Finally, we will discuss these concepts as they apply to different cell types such as neurons, cardiomyocytes, and corneal epithelial cells.

scholarly journals Cell death and cell protection genes determine the fate of pistils in maize

Development ◽  
1999 ◽  
Vol 126 (3) ◽  
pp. 435-441
Author(s):  
A. Calderon-Urrea ◽  
S.L. Dellaporta
Keyword(s):  
Cell Death ◽  
Sex Determination ◽  
Sexual Maturation ◽  
Temporal Pattern ◽  
Death Process ◽  
Cell Protection ◽  
Selective Elimination ◽  
Cell Death Process ◽  
A Cell ◽  
Unisexual Flowers

The formation of unisexual flowers in maize requires the selective elimination and sexual maturation of floral organs in an initially bisexual floral meristem. Elimination of pistil primordia occurs in the primary and secondary florets of the tassel spikelets, and in the secondary florets of ear spikelets. Ill-fated pistil cells undergo a cell death process associated with nuclear degeneration in a specific spatial-temporal pattern that begins in the subepidermis, eventually aborting the entire organ. The sex determination genes tasselseed1 and tasselseed2 are required for death of pistil cells. tasselseed1 is required for the accumulation of TASSELSEED2 mRNA in pistil cells. All pistil primordia express TASSELSEED2 RNA but functional pistils found in ear spikelets are protected from cell death by the action of the silkless1 gene. silkless1 blocks tasselseed-induced cell death in the pistil primordia of primary ear florets. A model is proposed for the control of pistil fate by the action of the ts1-ts2-sk1 pathway.

scholarly journals Homotypic cell cannibalism, a cell‐death process regulated by the nuclear protein 1, opposes to metastasis in pancreatic cancer

2012 ◽  
Vol 4 (9) ◽  
pp. 964-979 ◽  
Author(s):  
Carla E. Cano ◽  
María José Sandí ◽  
Tewfik Hamidi ◽  
Ezequiel L. Calvo ◽  
Olivier Turrini ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Death ◽  
Nuclear Protein ◽  
Death Process ◽  
Cell Death Process ◽  
A Cell

scholarly journals MORPHOLOGICAL AND BIOCHEMICAL CHARACTERIZATION OF A CELL DEATH PROCESS INDUCED BY E3, A NEW SYNTHETIC DIARYLSULFONILUREA ANALOGUE

2001 ◽  
Vol 1 (S3) ◽  
pp. 50-50
Author(s):  
M. Alonso ◽  
M. Miglaccio ◽  
I. Encio ◽  
A. Asumendi ◽  
V. Martinez-Merino ◽  
...  
Keyword(s):  
Cell Death ◽  
Biochemical Characterization ◽  
Death Process ◽  
Cell Death Process ◽  
A Cell

Protection from CMV infection in immunodeficient hosts by adoptive transfer of memory B cells

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3472-3479 ◽  
Author(s):  
Karin Klenovsek ◽  
Florian Weisel ◽  
Andrea Schneider ◽  
Uwe Appelt ◽  
Stipan Jonjic ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
B Cell ◽  
Therapeutic Potential ◽  
Severe Disease ◽  
Memory B Cells ◽  
Immune Defense ◽  
Cmv Infection ◽  
Antiviral Immune Response ◽  
A Cell

AbstractSevere disease associated with cytomegalovirus (CMV) infection is still a major problem in patients who undergo transplantation. Support of the patients' immune defense against the virus is a major goal in transplantation medicine. We have used the murine model of CMV (MCMV) to investigate the potential of a cell-based strategy to support the humoral antiviral immune response. Immunocompetent C57BL/6 mice were infected with MCMV, and memory B cells from the immune animals were adoptively transferred into T-cell– and B-cell–deficient RAG-1−/− mice. Following MCMV infection, a virus-specific IgG response developed within 4 to 7 days in the recipient animals. Concomitantly, a significant reduction in viral titers and DNA copies in several organs was observed. In addition, the memory B-cell transfer provided long-term protection from the lethal course of the infection that is invariably seen in immunodeficient animals. Transfer of memory B cells was also effective in protecting from an already ongoing viral infection, indicating a therapeutic potential of virus-specific memory B cells. T cells were not involved in this process. Our data provide evidence that a cell-based strategy to support the humoral immune response can be effective to combat infectious pathogens in severely immunodeficient hosts.

scholarly journals Morphological and Biochemical Characterization of a Cell Death Process Induced by E3, a New Synthetic Diarylsulfonilurea Analogue

2001 ◽  
Vol 1 ◽  
pp. 50-50
Author(s):  
M. Alonso ◽  
M. Miglaccio ◽  
I. Encío ◽  
A. Asumendi ◽  
V. Martinez-Merino ◽  
...  
Keyword(s):  
Cell Death ◽  
Biochemical Characterization ◽  
Death Process ◽  
Cell Death Process ◽  
A Cell

scholarly journals Homotypic cell cannibalism, a cell‐death process regulated by the nuclear protein 1, opposes to metastasis in pancreatic cancer

2021 ◽  
Vol 13 (5) ◽  
Author(s):  
Carla E Cano ◽  
María José Sandí ◽  
Tewfik Hamidi ◽  
Ezequiel L Calvo ◽  
Olivier Turrini ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Death ◽  
Nuclear Protein ◽  
Death Process ◽  
Cell Death Process ◽  
A Cell

scholarly journals 521. Similarities and Differences in Transcriptomic Host Response between SARS-CoV-2 and Other Viral Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S326-S327
Author(s):  
Simone A Thair ◽  
Yudong He ◽  
Yehudit Hasin-Brumshtein ◽  
Suraj Sakaram ◽  
Rushika R Pandya ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Nk Cells ◽  
Pathway Analysis ◽  
Host Response ◽  
Viral Infections ◽  
Cell Types ◽  
Gene Signature ◽  
Gene Signatures ◽  
Similarities And Differences

Abstract Background COVID-19 is a pandemic caused by the SARS-CoV-2 virus that shares and differs in clinical characteristics of known viral infections. Methods We obtained RNAseq profiles of 62 prospectively enrolled COVID-19 patients and 24 healthy controls (HC). We collected 23 independent studies profiling 1,855 blood samples from patients covering six viruses (influenza, RSV, HRV, Ebola, Dengue and SARS-CoV-1). We studied host whole-blood transcriptomic responses in COVID-19 compared to non-COVID-19 viral infections to understand similarities and differences in host response. Gene signature threshold was absolute effect size ≥1, FDR ≤ 0.05%. Results Differential gene expression of COVID-19 vs HC are highly correlated with non-COVID-19 vs HC (r=0.74, p< 0.001). We discovered two gene signatures: COVID-19 vs HC (2002 genes) (COVIDsig) and non-COVID-19 vs HC (635 genes) (nonCOVIDsig). Pathway analysis of over-expressed signature genes in COVIDsig or nonCOVIDsig identified similar pathways including neutrophil activation, innate immune response, immune response to viral infection and cytokine production. Conversely, for under-expressed genes, pathways indicated repression of lymphocyte differentiation and activation (Fig1). Intersecting the two gene signatures found two genes significantly oppositely regulated (ACO1, ATL3). We derived a third gene signature using COCONUT to compare COVID-19 to non-COVID-19 viral infections (416 genes) (Fig2). Pathway analysis did not result in significant enrichment, suggesting identification of novel biology (Fig1). Statistical deconvolution of bulk transcriptomic data found M1 macrophages, plasmacytoid dendritic cells, CD14+ monocytes, CD4+ T cells and total B cells changed in the same direction across COVID-19 and non-COVID-19 infections. Cell types that increased in COVID-19 relative to non-COVID-19 were CD56bright NK cells, M2 macrophages and total NK cells. Those that decreased in non-COVID-19 relative to COVID-19 were CD56dim NK cells & memory B cells and eosinophils (Fig3). Figure 1 Figure 2 Figure 3 Conclusion The concordant and discordant responses mapped here provide a window to explore the pathophysiology of COVID-19 vs other viral infections and show clear differences in signaling pathways and cellularity as part of the host response to SARS-CoV-2. Disclosures Simone A. Thair, PhD, Inflammatix, Inc. (Employee, Shareholder) Yudong He, PhD, Inflammatix Inc. (Employee) Yehudit Hasin-Brumshtein, PhD, Inflammatix (Employee, Shareholder) Suraj Sakaram, MS in Biochemistry and Molecular Biology, Inflammatix (Employee, Other Financial or Material Support, stock options) Rushika R. Pandya, MS, Inflammatix Inc. (Employee, Shareholder) David C. Rawling, PhD, Inflammatix Inc. (Employee, Shareholder) Purvesh Khatri, PhD, Inflammatix Inc. (Shareholder) Timothy Sweeney, MD, PHD, Inflammatix, Inc. (Employee, Shareholder)

scholarly journals Correction: PML induces a novel caspase-independent cell death process

10.1038/8706 ◽  
1999 ◽  
Vol 22 (1) ◽  
pp. 115-115 ◽  
Author(s):  
Fredérique Quignon
Keyword(s):  
Cell Death ◽  
Death Process ◽  
Cell Death Process
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