Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The recombination-activating genes (RAG) 1 and 2 are indispensable for diversifying the primary B cell receptor repertoire and pruning self-reactive clones via receptor editing in the bone marrow; however, the impact of RAG1/RAG2 on peripheral tolerance is unknown. Partial RAG deficiency (pRD) manifesting with late-onset immune dysregulation represents an 'experiment of nature' to explore this conundrum. By studying B cell development and subset-specific repertoires in pRD, we demonstrate that reduced RAG activity impinges on peripheral tolerance through the generation of a restricted primary B cell repertoire, persistent antigenic stimulation and an inflammatory milieu with elevated B cell-activating factor. This unique environment gradually provokes profound B cell dysregulation with widespread activation, remarkable extrafollicular maturation and persistence, expansion and somatic diversification of self-reactive clones. Through the model of pRD, we reveal a RAG-dependent 'domino effect' that impacts stringency of tolerance and B cell fate in the periphery.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355881 | PMC |
| http://dx.doi.org/10.1038/s41590-022-01271-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
European guideline informed RAG-based GPT-4 decision support tool in tumor board meetings for breast cancer treatment.
Eur J Surg Oncol
August 2025
Department of Radiology and Neuroradiology, GFO Clinics Troisdorf, Academic Hospital of the Friedrich-Wilhelms-University Bonn, 53840, Troisdorf, Germany. Electronic address:
Breast cancer is the most common cancer among women worldwide. Treatment decision-making in multidisciplinary tumor boards is complex, involving integration of clinical guidelines, patient data, and preferences. We retrospectively evaluated MammaBoardGPT, an few-shot in-context learning and Retrieval Augmented Generation (RAG) enhanced GPT-4 model with European guidelines and five Tumor Board labeled cases, against standard GPT-4 in 25 breast cancer cases discussed at a German hospital.
View Article and Find Full Text PDFFactors associated with and kinetics of anti-IFN-α autoantibodies in deficiency.
J Allergy Clin Immunol Glob
August 2025
Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St Petersburg, Fla.
Background: Autoantibodies against IFN-α (anti-IFN-α) have been reported in recombinase activating gene (RAG) deficiency, attributed to impaired central and peripheral T-cell/B-cell tolerance. However, the clinical features, especially viral infections, associated with these autoantibodies at baseline, their kinetics over time, and their response to hematopoietic cell transplantation are not well defined.
Objective: We described the clinical and immunologic findings linked to anti-IFN-α IgG in RAG deficiency and tracked its kinetics longitudinally, including in those who underwent hematopoietic cell transplantation.
Investigation of the DNA Methylation-Modified 8-17 DNAzyme Functions via Sensitive Catalytic Hairpin Self-Assembly Reaction.
ACS Sens
June 2025
School of Pharmaceutical Sciences, Guizhou University, Guiyang 550025, China.
8-17 DNAzyme is a well-known versatile nucleic acid tool for achieving a specific cleavage function, and thus, investigation of 8-17 DNAzyme functions can prove to be of great significance. The conventional epigenetic modification on DNAzyme may pave a new way for the study of catalytic properties. Herein, the most abundant and best characterized modifications 5-methylcytosine (5mC) and -methyladenosine (m6A) are introduced into the central catalytic core and stem sequence of 8-17 DNAzyme to evaluate the cleavage activity.
View Article and Find Full Text PDFImmunopathological and microbial signatures of inflammatory bowel disease in partial RAG deficiency.
J Exp Med
August 2025
Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Partial RAG deficiency (pRD) can manifest with systemic and tissue-specific immune dysregulation, with inflammatory bowel disease (IBD) in 15% of the patients. We aimed at identifying the immunopathological and microbial signatures associated with IBD in patients with pRD and in a mouse model of pRD (Rag1w/w) with spontaneous development of colitis. pRD patients with IBD and Rag1w/w mice showed a systemic and colonic Th1/Th17 inflammatory signature.
View Article and Find Full Text PDFImmunotherapy followed by cetuximab in locally advanced/metastatic cutaneous squamous cell carcinomas: the I-TACKLE trial.
Eur J Cancer
May 2025
Head and Neck Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, via Giacomo Venezian 1, Milan 20133, Italy; Department of Oncology and Hemato-oncology, University of Milan, via Santa Sofia 9/1, Milan 20122, Italy.
Background: Immunotherapy with pembrolizumab and cemiplimab achieves an overall response rate (ORR) of 34-51 % in locally advanced/metastatic (LA/M) cSCC, but primary and acquired resistance remains a challenge. This study evaluates whether adding cetuximab to pembrolizumab can overcome resistance by reducing immune escape.
Patients And Methods: I-TACKLE is a phase II, open-label trial conducted at three Italian centers.