Objective: The bcl-6 proto-oncogene is ubiquitously expressed in various tissues. Since we found out the smaller number of TER119(+) cells in the spleen of neonatal bcl-6-deficient (bcl-6(-/-)) mice compared with that of control (bcl-6(+/+)) littermates, we studied functions of bcl-6 in differentiation of erythroid lineage cells.
Materials And Methods: Erythroblasts in the definitive erythropoiesis were separated into four subsets using anti-TER119 and anti-CD71 mAbs. The cell number and property of these four subsets in spleens of neonatal bcl-6(+/+) and bcl-6(-/-) mice were examined using a flow cytometry.
Results: bcl-6 mRNA expression was detected in the TER119(high)CD71(high) subset, which is morphologically equivalent to basophilic erythroblasts, by reverse-transcribed polymerase chain reaction. High percentages of cells in the TER119(low)CD71(high) and TER119(high)CD71(high) subsets were in the cell cycle. The cell number of the TER119(high)CD71(high) subset in the spleen and the percentage of reticulocytes in the peripheral blood of neonatal bcl-6(-/-) mice were significantly lower than those of neonatal bcl-6(+/+) mice. However, the percentage of apoptotic cells and that of cells in the cell cycle in the TER119(high)CD71(high) subset of bcl-6(-/-) mice were similar to those of bcl-6(+/+) mice.
Conclusion: bcl-6 detected in the TER119(high)CD71(high) subset of erythroblasts in the spleen of neonatal mice may be required to retain the erythroblasts in the cell proliferation stage.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.exphem.2004.10.001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
T follicular helper cell is essential for M2 macrophage polarization and pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension.
Respir Res
December 2024
Department of Respiratory Diseases, Medical School, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People's Republic of China.
Article Synopsis
- The study investigates how T follicular helper cells and the cytokine IL-21 contribute to hypoxia-induced pulmonary hypertension (HPH), a condition that can lead to serious heart problems.
- Using mouse models, the research found that mice lacking IL-21 or with reduced T cells showed less severe pulmonary hypertension, suggesting that IL-21 plays a crucial role in the disease's progression.
- The findings revealed that chronic exposure to hypoxia increases germinal center B cell activity and promotes a shift in macrophages towards a phenotype that exacerbates vascular remodeling, showcasing potential targets for future therapies.
Spatial microniches of IL-2 combine with IL-10 to drive lung migratory T2 cells in response to inhaled allergen.
Nat Immunol
November 2024
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Article Synopsis
- - The study investigates how T helper 2 (T2) cells, involved in allergic reactions, differentiate in barrier tissues, focusing on house dust mite-specific T cells in mice.
- - Key to T2 cell differentiation and migration is the early expression of a protein called Blimp-1, with its absence hindering T2 cell development in the lungs.
- - The findings highlight the importance of IL-2 signaling and the local environment in lymph nodes, which support the initial formation of T2 cells by promoting Blimp-1 and GATA3, crucial for allergic asthma development.
Relocalizing transcriptional kinases to activate apoptosis.
Science
October 2024
Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
Kinases are critical regulators of cellular function that are commonly implicated in the mechanisms underlying disease. Most drugs that target kinases are molecules that inhibit their catalytic activity, but here we used chemically induced proximity to convert kinase inhibitors into activators of therapeutic genes. We synthesized bivalent molecules that link ligands of the transcription factor B cell lymphoma 6 (BCL6) to inhibitors of cyclin-dependent kinases (CDKs).
View Article and Find Full Text PDFCombination of bortezomib and venetoclax targets the pro-survival function of LMP-1 and EBNA-3C of Epstein-Barr virus in spontaneous lymphoblastoid cell lines.
PLoS Pathog
September 2024
Department of Pediatrics and Adolescent Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Epstein-Barr virus (EBV) manipulates the ubiquitin-proteasome system and regulators of Bcl-2 family to enable the persistence of the virus and survival of the host cells through the expression of viral proteins in distinct latency patterns. We postulate that the combination of bortezomib (proteasome inhibitor) and venetoclax (Bcl-2 inhibitor) [bort/venetoclax] will cause synergistic killing of post-transplant lymphoproliferative disorder (PTLD) through targeting the pro-survival function of latent viral proteins such as latent membrane protein-1 (LMP-1) and EBV nuclear antigen-3C (EBNA-3C). Bort/venetoclax could synergistically kill spontaneous lymphoblastoid cell lines (sLCLs) derived from patients with PTLD and EBV-associated hemophagocytic lymphohistiocytosis by inducing DNA damage response, apoptosis and G1-S cell cycle arrest in a ROS-dependent manner.
View Article and Find Full Text PDFDiscovery of novel BCL6-Targeting PROTACs with effective antitumor activities against DLBCL in vitro and in vivo.
Eur J Med Chem
November 2024
Shanghai Key Laboratory of Regulatory Biology, The Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, 200241, China; School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunna, 650500, China; Yunnan College of Modern Biomedical Industry, Kunming Medical University, Kunming, Yunnan, 650500, China. Electronic address:
The transcriptional repressor B cell lymphoma 6 (BCL6) plays a critical role in driving tumorigenesis of diffuse large B-cell lymphoma (DLBCL). However, the therapeutic potential of inhibiting or degrading BCL6 for DLBCL has not been thoroughly understood. Herein, we reported the discovery of a series of novel BCL6-targeting PROTACs based on our previously reported N-phenyl-4-pyrimidinamine BCL6 inhibitors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!