Intrinsic polyclonal B cell activation is characteristic of NZB mice and it contributes to the development of lupus nephritis in NZB crosses. Although multiple autosomal genes appear to be involved, the major loci for B cell hyperactivity have been mapped on chromosome 4. To identify various genes determining B cell hyperactivity, differential mRNA display was done comparing B cells of NZB and BALB/c mice. The approach yielded 32 genes that were consistently upregulated in NZB B cells. Among these, alpha-enolase, which is located in the region of chromosome 4 containing B cell hyperactivity loci, was found to be spontaneously overexpressed only in NZB B cells, but not in splenic B or T cells of BALB/c or T cells of NZB mice. Exposure to soluble, but not plate-bound, enolase induced splenic B cells from normal BALB/c mice or B cell lymphoma lines to secrete Ig that was mediated by augmented transcription. Moreover, in combination with a subthreshold stimulus with anti-IgM, enolase augmented the expression of CD69 and B7.2 in nai;ve B cells from normal mice. Enolase probably functions intracellularly as an accessory molecule in stimulating B cells. Since functionally related genes tend to congregate, enolase may contribute to polyclonal B cell activation in cooperation with other genes in the hyperactivity loci, which appear to be in a transcriptionally active region in NZB B cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1006/clim.2002.5261 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
N-methyl-D-aspartate Receptors and Depression: Linking Psychopharmacology, Pathology and Physiology in a Unifying Hypothesis for the Epigenetic Code of Neural Plasticity.
Pharmaceuticals (Basel)
November 2024
Relmada Therapeutics, Inc., Coral Gables, FL 33134, USA.
Uncompetitive NMDAR (N-methyl-D-aspartate receptor) antagonists restore impaired neural plasticity, reverse depressive-like behavior in animal models, and relieve major depressive disorder (MDD) in humans. This review integrates recent findings from in silico, in vitro, in vivo, and human studies of uncompetitive NMDAR antagonists into the extensive body of knowledge on NMDARs and neural plasticity. Uncompetitive NMDAR antagonists are activity-dependent channel blockers that preferentially target hyperactive GluN2D subtypes because these subtypes are most sensitive to activation by low concentrations of extracellular glutamate and are more likely activated by certain pathological agonists and allosteric modulators.
View Article and Find Full Text PDFTLR7 Promotes Acute Inflammatory-Driven Lung Dysfunction in Influenza-Infected Mice but Prevents Late Airway Hyperresponsiveness.
Int J Mol Sci
December 2024
Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia.
Severe lower respiratory tract disease following influenza A virus (IAV) infection is characterized by excessive inflammation and lung tissue damage, and this can impair lung function. The effect of toll-like receptor 7 (TLR7), which detects viral RNA to initiate antiviral and proinflammatory responses to IAV, on lung function during peak infection and in the resolution phase is not fully understood. Using wild-type (WT) C57BL/6 and TLR7 knockout (TLR7 KO) mice, we found that IAV infection induced airway dysfunction in both genotypes, although in TLR7 KO mice, this dysfunction manifested later, did not affect lung tissue elastance and damping, and was associated with a different immune phenotype.
View Article and Find Full Text PDFAlterations in Striatal Architecture and Biochemical Markers' Levels During Postnatal Development in the Rat Model of an Attention Deficit/Hyperactivity Disorder (ADHD).
Int J Mol Sci
December 2024
Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, Warszawska 30, 10-082 Olsztyn, Poland.
Attention deficit/hyperactivity disorder (ADHD) is defined as a neurodevelopmental condition. The precise underlying mechanisms remain incompletely elucidated. A body of research suggests disruptions in both the cellular architecture and neuronal function within the brain regions of individuals with ADHD, coupled with disturbances in the biochemical parameters.
View Article and Find Full Text PDFThe Use of Nutraceutical and Pharmacological Strategies in Murine Models of Autism Spectrum Disorder.
Cells
December 2024
Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy.
Autism spectrum disorder (ASD) is a common neurodevelopmental condition mainly characterized by both a scarce aptitude for social interactions or communication and engagement in repetitive behaviors. These primary symptoms can manifest with variable severity and are often paired with a heterogeneous plethora of secondary complications, among which include anxiety, ADHD (attention deficit hyperactivity disorder), cognitive impairment, sleep disorders, sensory alterations, and gastrointestinal issues. So far, no treatment for the core symptoms of ASD has yielded satisfactory results in a clinical setting.
View Article and Find Full Text PDFNeuronal cell type specific roles for Nprl2 in neurodevelopmental disorder-relevant behaviors.
Neurobiol Dis
January 2025
The University of Texas Southwestern Medical Center, Department of Neurology, Dallas, TX, United States of America; The University of Texas Southwestern Medical Center, Department of Psychiatry, Dallas, TX, United States of America; The University of Texas Southwestern Medical Center, Department of Pediatrics, Dallas, TX, United States of America; The University of Texas Southwestern Medical Center, Department of Neuroscience, Dallas, TX, United States of America. Electronic address:
Loss of function in the subunits of the GTPase-activating protein (GAP) activity toward Rags-1 (GATOR1) complex, an amino-acid sensitive negative regulator of the mechanistic target of rapamycin complex 1 (mTORC1), is implicated in both genetic familial epilepsies and NDDs (Baldassari et al., 2018). Previous studies have found seizure phenotypes and increased activity resulting from conditional deletion of GATOR1 function from forebrain excitatory neurons (Yuskaitis et al.
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!