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Autoimmune diseases (AIDs) constitute a group of disorders where the immune system mistakenly attacks the body's tissues. The pathogenesis of AIDs involve a breakdown in immune tolerance, culminating in an immune response that targets autoantigens. In adaptive immunity, secondary rearrangement of T cell receptors (TCRs) and B cell receptors (BCRs) involves sequential V(D)J recombination events during lymphocyte development. Imperfect receptor editing during this process can generate autoreactive clones, thereby contributing to the pathogenesis of AIDs. Emerging evidence implicates secondary V(D)J recombination in TCR and BCR genes as a pathogenic driver in multiple AIDs. The detection of secondary rearrangements, along with targeted therapeutic interventions (e.g. anti-CD40L, IL6), offers novel avenues for the early prediction and diagnosis of these diseases. This article provides a comprehensive overview of the current research on the role of TCR/BCR secondary rearrangements in AIDs, elucidating their mechanisms of action to enhance our understanding of the pathogenesis, diagnosis, and treatment of autoimmune disorders.
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http://dx.doi.org/10.1080/08820139.2025.2556781 | DOI Listing |
Immunol Invest
September 2025
Scientific Research Department, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
Autoimmune diseases (AIDs) constitute a group of disorders where the immune system mistakenly attacks the body's tissues. The pathogenesis of AIDs involve a breakdown in immune tolerance, culminating in an immune response that targets autoantigens. In adaptive immunity, secondary rearrangement of T cell receptors (TCRs) and B cell receptors (BCRs) involves sequential V(D)J recombination events during lymphocyte development.
View Article and Find Full Text PDFFront Immunol
May 2025
School of Public Health and Health Management, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Introduction: The high percentage of Omicron breakthrough infection in vaccinees is an emerging problem, of which we have a limited understanding of the phenomenon.
Methods: We performed single-cell transcriptome coupled with T-cell/B-cell receptor (TCR/BCR) sequencing in 15 peripheral blood mononuclear cell (PBMC) samples from Omicron infection and naïve with booster vaccination.
Results: We found that after breakthrough infection, multiple cell clusters showed activation of the type I IFN pathway and widespread expression of Interferon-stimulated genes (ISGs); T and B lymphocytes exhibited antiviral and proinflammatory-related differentiation features with pseudo-time trajectories; and large TCR clonal expansions were concentrated in effector CD8 T cells, and clonal expansions of BCRs showed a preference for IGHV3.
Cancer Rep (Hoboken)
July 2023
Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
Background: Several clinical trials of nivolumab have reported good results, including those in patients with advanced esophageal squamous cell carcinoma. However, the response rate of this drug remains poor. Notably, a rare phenomenon called abscopal effect refers to the regression of irradiated and nonirradiated distant tumors after local radiotherapy.
View Article and Find Full Text PDFEmerg Microbes Infect
December 2023
Division of Cardiology, Shanghai Immune Therapy Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Over 3 billion doses of inactivated vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been administered globally. However, our understanding of the immune cell functional transcription and T cell receptor (TCR)/B cell receptor (BCR) repertoire dynamics following inactivated SARS-CoV-2 vaccination remains poorly understood. Here, we performed single-cell RNA and TCR/BCR sequencing on peripheral blood mononuclear cells at four time points after immunization with the inactivated SARS-CoV-2 vaccine BBIBP-CorV.
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June 2022
CNRS and Strasbourg University, Unit Biotechnology and Cell signaling, UMR7242/Strasbourg Drug Discovery and Development Institute (IMS), Strasbourg, France.
In systemic lupus erythematosus, T cells display multiple abnormalities. They are abnormally activated, secrete pro-inflammatory cytokines, help B cells to generate pathogenic autoantibodies, and provoke the accumulation of autoreactive memory T cells. P140, a synthetic peptide evaluated in phase-III clinical trials for lupus, binds HSPA8/HSC70 chaperone protein.
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