scholarly journals Cytoskeleton protein 4.1R regulates B‐cell fate by modulating the canonical NF‐ κ B pathway

Immunology ◽  
2020 ◽  
Vol 161 (4) ◽  
pp. 314-324
Author(s):  
Taotao Liang ◽  
Yuying Guo ◽  
Mengjia Li ◽  
Cong Ding ◽  
Siyao Sang ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Fate ◽  
Cytoskeleton Protein ◽  
Protein 4.1R

scholarly journals EBF1 is expressed in pericytes and contributes to pericyte cell commitment

2021 ◽  
Author(s):  
Francesca Pagani ◽  
Elisa Tratta ◽  
Patrizia Dell’Era ◽  
Manuela Cominelli ◽  
Pietro Luigi Poliani
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
B Cell ◽  
Cell Fate ◽  
Early Stage ◽  
Cell Lineage ◽  
Cell Maturation ◽  
Cell Commitment

AbstractEarly B-cell factor-1 (EBF1) is a transcription factor with an important role in cell lineage specification and commitment during the early stage of cell maturation. Originally described during B-cell maturation, EBF1 was subsequently identified as a crucial molecule for proper cell fate commitment of mesenchymal stem cells into adipocytes, osteoblasts and muscle cells. In vessels, EBF1 expression and function have never been documented. Our data indicate that EBF1 is highly expressed in peri-endothelial cells in both tumor vessels and in physiological conditions. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS) analysis suggest that EBF1-expressing peri-endothelial cells represent bona fide pericytes and selectively express well-recognized markers employed in the identification of the pericyte phenotype (SMA, PDGFRβ, CD146, NG2). This observation was also confirmed in vitro in human placenta-derived pericytes and in human brain vascular pericytes (HBVP). Of note, in accord with the key role of EBF1 in the cell lineage commitment of mesenchymal stem cells, EBF1-silenced HBVP cells showed a significant reduction in PDGFRβ and CD146, but not CD90, a marker mostly associated with a prominent mesenchymal phenotype. Moreover, the expression levels of VEGF, angiopoietin-1, NG2 and TGF-β, cytokines produced by pericytes during angiogenesis and linked to their differentiation and activation, were also significantly reduced. Overall, the data suggest a functional role of EBF1 in the cell fate commitment toward the pericyte phenotype.

Pax5 determines B- versus T-cell fate and does not block early myeloid-lineage development

Blood ◽  
2003 ◽  
Vol 101 (11) ◽  
pp. 4342-4346 ◽  
Author(s):  
Claudiu V. Cotta ◽  
Zheng Zhang ◽  
Hyung-Gyoon Kim ◽  
Christopher A. Klug
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Fate ◽  
Nk Cell ◽  
Cell Lineage ◽  
Blood Analysis ◽  
Hematopoietic Stem ◽  
Peripheral Blood Analysis

Abstract Progenitor B cells deficient in Pax5 are developmentally multipotent, suggesting that Pax5 is necessary to maintain commitment to the B-cell lineage. Commitment may be mediated, in part, by Pax5 repression of myeloid-specific genes. To determine whether Pax5 expression in multipotential cells is sufficient to restrict development to the B-cell lineage in vivo, we enforced expression of Pax5 in hematopoietic stem cells using a retroviral vector. Peripheral blood analysis of all animals reconstituted with Pax5-expressing cells indicated that more than 90% of Pax5-expressing cells were B220+ mature B cells that were not malignant. Further analysis showed that Pax5 completely blocked T-lineage development in the thymus but did not inhibit myelopoiesis or natural killer (NK) cell development in bone marrow. These results implicate Pax5 as a critical regulator of B- versus T-cell developmental fate and suggest that Pax5 may promote commitment to the B-cell lineage by mechanisms that are independent of myeloid gene repression.

scholarly journals Regulation of B cell fate specification and V H gene rearrangements by Ikaros

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Damien REYNAUD ◽  
Karen REDDY ◽  
Hilde SCHJERVEN ◽  
Chauncey SPOONER ◽  
Eric BERTOLINO ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Fate ◽  
Gene Rearrangements ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
H Gene

MicroRNA-directed pathway discovery elucidates an miR-221/222–mediated regulatory circuit in class switch recombination

2021 ◽  
Vol 218 (11) ◽  
Author(s):  
Eric J. Wigton ◽  
Yohei Mikami ◽  
Ryan J. McMonigle ◽  
Carlos A. Castellanos ◽  
Adam K. Wade-Vallance ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Fate ◽  
Cell Activation ◽  
Class Switch Recombination ◽  
Cell Fate Decisions ◽  
Class Switch ◽  
Mrna Targets ◽  
Regulatory Circuit ◽  
Pathway Discovery

MicroRNAs (miRNAs, miRs) regulate cell fate decisions by post-transcriptionally tuning networks of mRNA targets. We used miRNA-directed pathway discovery to reveal a regulatory circuit that influences Ig class switch recombination (CSR). We developed a system to deplete mature, activated B cells of miRNAs, and performed a rescue screen that identified the miR-221/222 family as a positive regulator of CSR. Endogenous miR-221/222 regulated B cell CSR to IgE and IgG1 in vitro, and miR-221/222–deficient mice exhibited defective IgE production in allergic airway challenge and polyclonal B cell activation models in vivo. We combined comparative Ago2-HITS-CLIP and gene expression analyses to identify mRNAs bound and regulated by miR-221/222 in primary B cells. Interrogation of these putative direct targets uncovered functionally relevant downstream genes. Genetic depletion or pharmacological inhibition of Foxp1 and Arid1a confirmed their roles as key modulators of CSR to IgE and IgG1.

Epigenetic regulation of B cell fate and function during an immune response

2019 ◽  
Vol 288 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Yan Zhang ◽  
Kim L. Good‐Jacobson
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Cell Fate ◽  
Epigenetic Regulation ◽  
And Function

scholarly journals Restriction of memory B cell differentiation at the germinal center B cell positive selection stage

2020 ◽  
Vol 217 (7) ◽  
Author(s):  
Amparo Toboso-Navasa ◽  
Arief Gunawan ◽  
Giulia Morlino ◽  
Rinako Nakagawa ◽  
Andrea Taddei ◽  
...  
Keyword(s):  
B Cells ◽  
Positive Selection ◽  
B Cell ◽  
Cell Fate ◽  
Germinal Center ◽  
Target Genes ◽  
Zinc Finger Protein ◽  
B Cell Differentiation ◽  
Repressor Complex ◽  
Selection Stage

Memory B cells (MBCs) are key for protection from reinfection. However, it is mechanistically unclear how germinal center (GC) B cells differentiate into MBCs. MYC is transiently induced in cells fated for GC expansion and plasma cell (PC) formation, so-called positively selected GC B cells. We found that these cells coexpressed MYC and MIZ1 (MYC-interacting zinc-finger protein 1 [ZBTB17]). MYC and MIZ1 are transcriptional activators; however, they form a transcriptional repressor complex that represses MIZ1 target genes. Mice lacking MYC–MIZ1 complexes displayed impaired cell cycle entry of positively selected GC B cells and reduced GC B cell expansion and PC formation. Notably, absence of MYC–MIZ1 complexes in positively selected GC B cells led to a gene expression profile alike that of MBCs and increased MBC differentiation. Thus, at the GC positive selection stage, MYC–MIZ1 complexes are required for effective GC expansion and PC formation and to restrict MBC differentiation. We propose that MYC and MIZ1 form a module that regulates GC B cell fate.

scholarly journals BOB.1 controls memory B-cell fate in the germinal center reaction

2019 ◽  
Vol 101 ◽  
pp. 131-144 ◽  
Author(s):  
Maartje J. Levels ◽  
Cynthia M. Fehres ◽  
Lisa G.M. van Baarsen ◽  
Nathalie O.P. van Uden ◽  
Kristine Germar ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Fate ◽  
Germinal Center ◽  
Memory B Cell ◽  
Germinal Center Reaction

scholarly journals Autophagy and apoptosis are regulated by stress on Bcl2 by AMBRA1 in the endoplasmic reticulum and mitochondria

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Bojie Yang ◽  
Quansheng Liu ◽  
Yuanhong Bi
Keyword(s):  
Endoplasmic Reticulum ◽  
B Cell ◽  
Cell Fate ◽  
Cell Lymphoma ◽  
Feedback Regulation ◽  
B Cell Lymphoma ◽  
Regulatory Mechanisms ◽  
Time Duration ◽  
Cell Fate Decisions ◽  
Different Levels

Abstract Background Autophagy and apoptosis are two important physiological processes that determine cell survival or death in response to different stress signals. The regulatory mechanisms of these two processes share B-cell lymphoma-2 family proteins and AMBRA1, which are present in both the endoplasmic reticulum and mitochondria. B-cell lymphoma-2 family proteins sense different stresses and interact with AMBRA1 to regulate autophagy and apoptosis, which are respectively mediated by Beclin1 and Caspases. Therefore, we investigated how different levels of stress on B-cell lymphoma-2 family proteins that bind to AMBRA1 in the endoplasmic reticulum and mitochondria regulate the switch from autophagy to apoptosis. Methods In this paper, we considered the responses of B-cell lymphoma-2 family proteins, which bind to AMBRA1 in both the endoplasmic reticulum and mitochondria, to two different levels of stress in a model originally proposed by Kapuy et al. We investigated how these two stress levels affect the transition from autophagy to apoptosis and their effects on apoptosis activation over time. Additionally, we analyzed how the feedback regulation in this model affects the bifurcation diagrams of two levels of stress and cell fate decisions between autophagy and apoptosis. Results Autophagy is activated for minor stress in mitochondria regardless of endoplasmic reticulum stress, while apoptosis is activated for only significant stress in mitochondria. Apoptosis is only sensitive to mitochondria stress. The time duration before apoptosis activation is longer in the presence of high AMBRA1 levels with high endoplasmic reticulum and mitochondria stress. AMBRA1 can compete with B-cell lymphoma-2 family proteins to bind and activate Beclin1 and thus promote the autophagy process for a long time before apoptosis. Furthermore, apoptosis is prone to occur with increasing activation of Caspases, inactivation of Beclin1-A and the Michaelis constant of Caspases. Conclusion A novel mathematical model has been developed to understand the complex regulatory mechanisms of autophagy and apoptosis. Our model may be applied to further autophagy-apoptosis dynamic modeling experiments and simulations.

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