We have identified two intronic regions of mouse prdm1, the gene encoding B lymphocyte-induced maturation protein-1 (Blimp-1), which confer transcriptional repression in response to Bcl-6. The Bcl-6 response element in intron 5, which is conserved between mice and humans, was studied in detail. It binds Bcl-6 in vitro and was shown by chromatin immunoprecipitation to be occupied by Bcl-6 in vivo. Neither Bcl-6 response element functions as a STAT3-response element, showing that STAT3 does not compete with Bcl-6 at these sites. Bcl-6(-/-) mice confirm the biological importance of Bcl-6-dependent repression of prdm1. These mice have elevated Ab response, increased Ig-secreting cells, and increased Blimp-1(+) cells in spleen following immunization and their splenic B cells show accelerated plasmacytic development in vitro.
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http://dx.doi.org/10.4049/jimmunol.173.2.1158 | DOI Listing |
Cell Biol Toxicol
October 2024
Department of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510260, China.
Intervertebral disc degeneration (IVDD) is a primary contributor to low back pain and poses a considerable burden to society. However, the molecular mechanisms underlying IVDD remain to be elucidated. PR/SET domain 1 (PRDM1) regulates cell proliferation, apoptosis, and inflammatory responses in various diseases.
View Article and Find Full Text PDFNat Immunol
November 2024
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Cell Rep
August 2024
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA; The Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. Electronic address:
During chronic infection, virus-specific CD8 cytotoxic T lymphocytes (CTLs) progressively lose their ability to mount effective antiviral responses. This "exhaustion" is coupled to persistent upregulation of inhibitory receptor programmed death-1 (PD-1) (Pdcd1)-key in suppressing antiviral CTL responses. Here, we investigate allelic Pdcd1 subnuclear localization and transcription during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection in mice.
View Article and Find Full Text PDFJ Endocrinol Invest
December 2024
Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an City, 710061, Shaanxi, China.
Background: The deubiquitinating enzyme Ubiquitin-specific peptidase 15 (USP15) is upregulated in various cancers and promotes tumor progression by increasing the expression of several oncogenes. This project is designed to explore the role and mechanism of USP15 in thyroid cancer (TC) progression.
Methods: Selenium-binding protein 1 (SELENBP1), USP15, CCL2/5, CXCL10/11, IL-4, and TGF-β1 mRNA levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR).
EMBO J
May 2024
Department of Biochemistry, Tohoku University Graduate School of Medicine, Seiryo-machi 2-1, Sendai, 980-8575, Japan.
Transcription factors BACH2 and IRF4 are both essential for antibody class-switch recombination (CSR) in activated B lymphocytes, while they oppositely regulate the differentiation of plasma cells (PCs). Here, we investigated how BACH2 and IRF4 interact during CSR and plasma-cell differentiation. We found that BACH2 organizes heterochromatin formation of target gene loci in mouse splenic B cells, including targets of IRF4 activation such as Aicda, an inducer of CSR, and Prdm1, a master plasma-cell regulator.
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