Article
Immunology
Artem Krantsevich, Catherine Tang, Thomas MacCarthy
Summary: Somatic hypermutation (SHM) of Immunoglobulin (Ig) genes is crucial for antibody affinity maturation in B cells, with the mutagenic enzyme activation induced deaminase (AID) and DNA polymerase eta (Pol eta) playing key roles in introducing mutations at specific hotspots. By studying correlations between mutation sites, it was found that short-range interactions are dominated by AID and/or Pol eta overlapping hotspots, particularly in highly mutating IGHV sub-regions like CDRs. The results suggest that the hotspot preferences for AID and Pol eta have evolved to allow for greater interactions between induced mutations, shedding light on the mechanisms behind antibody affinity maturation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Ralf Kueppers, Bettina Budeus, Sylvia Hartmann, Martin-Leo Hansmann
Summary: CD30(+) B cells represent a distinct B-cell differentiation stage with features of strong activation. Studies have found that CD30(+) B cells can be more numerous in some cases of reactive lymphadenitis, and they are a heterogeneous population of polyclonal B cells, including both mutated and unmutated B-cells. These cell-rich CD30(+) B-cell populations do not represent precursor lesions of Hodgkin lymphoma.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Ophelie A. Martin, Morgane Thomas, Marie Marquet, Charlotte Bruzeau, Armand Garot, Mylene Brousse, Sebastien Bender, Claire Carrion, Jee Eun Choi, Bao Q. Vuong, Patricia J. Gearhart, Robert W. Maul, Sandrine Le Noir, Eric Pinaud
Summary: This study found that the scaffold/matrix attachment regions (5'- and 3'-MARs(E mu)) flanking the intronic core enhancer (cE mu) within the immunoglobulin heavy chain locus (IgH) are conserved in mice and humans, but their physiological role in somatic hypermutation (SHM) is still unclear. The results showed that deletion of MARs(E mu) led to an inverted substitution pattern in SHM, with a decrease upstream from cE mu and an increase downstream of it. This defect was not due to a direct transcription-coupled effect, but rather the consequence of a defect in base excision repair-associated unfaithful repair process. The study revealed an unexpected function of MARs(E mu) in limiting the error-prone repair machinery to the variable region of Ig gene loci.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Leticia K. Lerner, Dorine Bonte, Morwenna Le Guillou, Mahwish Mian Mohammad, Zeinab Kasraian, Alain Sarasin, Emmanuelle Despras, Said Aoufouchi
Summary: Somatic hypermutation is a B cell specific process that relies on the activity of activation-induced cytidine deaminase and DNA repair factors to generate specific and high affinity antibodies. This study reports the establishment of a modified human B cell line that recapitulates the mechanism of somatic hypermutation in vitro.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Hadas Neuman, Jessica Arrouasse, Meirav Kedmi, Andrea Cerutti, Giuliana Magri, Ramit Mehr
Summary: This article introduces a tool called IgTreeZ, which analyzes Ig gene lineage trees and their repertoires, and demonstrates its reliability in mutation and selection analysis through simulations. Researchers used IgTreeZ on empirical data and found different mutation patterns in different B cell subpopulations, as well as gained insights into antigen-driven selection in COVID-19 patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Kenneth B. Hoehn, Jackson S. Turner, Frederick Miller, Ruoyi Jiang, Oliver G. Pybus, Ali H. Ellebedy, Steven H. Kleinstein
Summary: The study found that after seasonal influenza vaccination, GC B cell lineages often exhibit measurable evolution, suggesting that the poor efficacy of seasonal influenza vaccines is not solely due to the inhibition of vaccine-specific B cell evolution.
Article
Multidisciplinary Sciences
Talin Ebrahimian, France Dierick, Vincent Ta, Maria Kotsiopriftis, Jonathan O'Connor Miranda, Koren K. Mann, Alexandre Orthwein, Stephanie Lehoux
Summary: Naive B cells producing IgM have a protective effect against atherosclerosis, while mature B cells producing class-switched antibodies promote atherosclerosis. Activation-induced cytidine deaminase (AID), which mediates class switch recombination (CSR), plays a significant role in both atherosclerosis and B cell tolerance. Depletion of AID inhibits atherosclerotic plaque formation.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Zhi Duan, Linda B. Baughn, Xiaohua Wang, Yongwei Zhang, Varun Gupta, Thomas MacCarthy, Matthew D. Scharff, Guojun Yu
Summary: The study shows that H3K79me2/3 and Dot1L are more abundant on the V region of Ig genes compared to the C region, with their knockout significantly reducing V region mutation and H3K79me2/3 levels. Knockout of Dot1L also leads to decreased Pol II levels and S2 phosphorylation at the IgH locus, along with reduced abundance of BRD4 and CDK9 on the V region. Treatment with inhibitors of BRD4 or CDK9 also affects SHM and Pol II S2P levels at the IgH locus, highlighting the importance of chromatin context and transcription dynamics in SHM.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Electra Sofou, Laura Zaragoza-Infante, Nikolaos Pechlivanis, Georgios Karakatsoulis, Sofia Notopoulou, Niki Stavroyianni, Fotis Psomopoulos, Elisavet Georgiou, Anne Langlois de Septenville, Frederic Davi, Andreas Agathangelidis, Anastasia Chatzidimitriou, Kostas Stamatopoulos
Summary: Classification of CLL patients based on the status of somatic hypermutation (SHM) of IGHV gene can provide predictive and prognostic relevance. However, the current method of evaluating SHM may underestimate its actual impact by overlooking the critical region for antigen-antibody interactions. This study discovered the presence of SHM within VH CDR3 of CLL patients with 'truly unmutated' IGHV genes.
FRONTIERS IN ONCOLOGY
(2022)
Article
Immunology
Morgane Thomas, Charlotte Bruzeau, Ophelie Alyssa Martin, Justine Pollet, Sebastien Bender, Claire Carrion, Sandrine Le Noir, Eric Pinaud
Summary: SATB1 is a cell type-specific factor that plays an essential role in the genetic network of developing T cells and neurons. However, its involvement in B-cell differentiation needs further clarification. Our study using a SATB1 knockout mouse model reveals that SATB1 is dispensable for B-cell development and the establishment of a broad IgH repertoire. We also find that SATB1 has a dual function in mature B cells, acting as a positive regulator in naive cells and a negative regulator in activated cells.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Computer Science, Artificial Intelligence
Ze Zhang, Woo Yong Chang, Kaiwen Wang, Yuqiu Yang, Xinlei Wang, Chen Yao, Tuoqi Wu, Li Wang, Tao Wang
Summary: This study investigates the relationship between B-cell receptors (BCRs) and B-cell gene expression in COVID-19. The researchers found a stronger coupling between BCRs and B-cell gene expression during COVID-19 infections. They developed the Benisse model, which revealed a gradient of B-cell activation along BCR trajectories.
NATURE MACHINE INTELLIGENCE
(2022)
Article
Hematology
Pablo Elias Morande, Xiao-Jie Yan, Julieta Sepulveda, Noe Seija, Maria Elena Marquez, Natalia Sotelo, Cecilia Abreu, Martina Crispo, Gabriel Fernandez-Grana, Natalia Rego, Therence Bois, Stephen P. Methot, Florencia Palacios, Victoria Remedi, Kanti R. Rai, Alejandro Buschiazzo, Javier M. Di Noia, Marcelo A. Navarrete, Nicholas Chiorazzi, Pablo Oppezzo
Summary: The study used chronic lymphocytic leukemia as a model and found a direct link between aberrant AID activity and cancer progression, whereby AID promotes aggressiveness in CLL and other B-cell neoplasms by selecting for CLL driver mutations with their oncogenic effects.
Article
Oncology
Meng Wu, Jing Zhang, Yi Wang, Lan Mi, Xiaopei Wang, Weiping Liu, Jie Fu, Haifeng Song, Yuqin Song, Jun Zhu
Summary: This study provides evidence that the presence of residual malignant B cells is connected to the clonal diversity of the resulting BCR repertoire. The study suggests that the growth rate of a patient's peripheral B cell diversity after stem cell transplant can be used as a prognostic indicator for relapse. The study also highlights the impact of tumor cells on the replenishment of the peripheral BCR immune repertoire.
Article
Immunology
Marina Alexeeva, Marivi Nabong Moen, Xiang Ming Xu, Anette Rasmussen, Ingar Leiros, Finn Kirpekar, Arne Klungland, Lene Alsoe, Hilde Nilsen, Svein Bjelland
Summary: Uracil arises in DNA through deamination and replication errors, and its repair by uracil-DNA glycosylase and the base excision repair pathway are crucial in maintaining genomic stability. The mechanisms of DNA incision following uracil excision are still uncertain, but it has been shown that hUNG may play a role in this process and contribute to class switch recombination activity in cells deficient in other repair enzymes.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Hiroyuki Yoshitomi
Summary: Tph cells, characterized by CXCL13 production and efficient help to B cells, play important roles in the pathogenesis of RA and other diseases such as autoimmune diseases, infectious diseases, and cancers.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alexander Goncearenco, Stephanie L. Rager, Minghui Li, Qing-Xiang Sang, Igor B. Rogozin, Anna R. Panchenko
NUCLEIC ACIDS RESEARCH
(2017)
Article
Multidisciplinary Sciences
Cyril Le Nouen, Thomas McCarty, Michael Brown, Melissa Laird Smith, Roberto Lleras, Michael A. Dolan, Masfique Mehedi, Lijuan Yang, Cindy Luongo, Bo Liang, Shirin Munir, Joshua M. DiNapoli, Steffen Mueller, Eckard Wimmer, Peter L. Collins, Ursula J. Buchholz
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Review
Cell Biology
Yang Yang, Yanzhe Gao, Anastasia Zlatanou, Satoshi Tateishi, Vyacheslav Yurchenko, Igor B. Rogozin, Cyrus Vaziri
Article
Multidisciplinary Sciences
Frida Belinky, Vladimir N. Babenko, Igor B. Rogozin, Eugene Koonin
SCIENTIFIC REPORTS
(2018)
Article
Multidisciplinary Sciences
Frida Belinky, Igor B. Rogozin, Eugene V. Koonin
SCIENTIFIC REPORTS
(2017)
Article
Multidisciplinary Sciences
Eugenia Poliakov, Joseph Soucy, Susan Gentleman, Igor B. Rogozin, T. Michael Redmond
SCIENTIFIC REPORTS
(2017)
Article
Oncology
Igor B. Rogozin, Abiel Roche-Lima, Artem G. Lada, Frida Belinky, Ivan A. Sidorenko, Galina Glazko, Vladimir N. Babenko, David N. Cooper, Youri Pavlov
Article
Microbiology
Matthias Lingemann, Thomas McCarty, Xueqiao Liu, Ursula J. Buchholz, Sonja Surman, Scott E. Martin, Peter L. Collins, Shirin Munir
Editorial Material
Multidisciplinary Sciences
Stanislav G. Kozmin, Igor B. Rogozin, Elizabeth A. Moore, Mariah Abney, Roel M. Schaaper, Youri I. Pavlov
Article
Biochemistry & Molecular Biology
Sheetal Uppal, Igor B. Rogozin, T. Michael Redmond, Eugenia Poliakov
Article
Microbiology
Igor B. Rogozin, Arzuv Charyyeva, Ivan A. Sidorenko, Vladimir N. Babenko, Vyacheslav Yurchenko
Article
Biochemistry & Molecular Biology
Frida Belinky, Ishan Ganguly, Eugenia Poliakov, Vyacheslav Yurchenko, Igor B. Rogozin
Summary: Nonsense mutations change a meaningful codon into a stop codon, resulting in a shortened protein product. In-frame stop codons are common in bacterial protein-coding genes but are not necessarily pseudogenes, as they are evolutionarily conserved. Double substitutions in codons show higher evolution rates, suggesting that in-frame stop codons can be introduced and reversed via positive selection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Cyril Le Nouen, Thomas McCarty, Lijuan Yang, Michael Brown, Eckard Wimmer, Peter L. Collins, Ursula J. Buchholz
Summary: Recoding viral genomes through codon-pair deoptimization (CPD) can provide new types of live-attenuated vaccine candidates, with a large number of nucleotide changes contributing to genetic stability. A study on a CPD-modified human respiratory syncytial virus, Min B, revealed that after multiple passages, the virus generated viral genomes with large internal deletions that relocated genes and promoted replication and expression. This study sheds light on the adaptability of a debilitated negative-strand RNA virus and the generation of defective minihelper viruses to overcome restrictions, a phenomenon not previously reported in RNA viruses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Microbiology
Igor B. Rogozin, Andreu Saura, Anastassia Bykova, Vyacheslav Brover, Vyacheslav Yurchenko
Summary: The analysis of deletions in the SARS-CoV-2 genome reveals evolutionary trends and sheds light on the virus's surprising variability and rapid spreading capability. The study focuses on understanding the molecular mechanisms of deletions and their correlation with repetitive elements. The findings suggest a possible hypervariability in certain accessory genes, which could potentially lead to new and more successful variants of the virus.
Article
Biochemistry & Molecular Biology
Sheetal Uppal, Olga Postnikova, Rafael Villasmil, Igor B. Rogozin, Alexander V. Bocharov, Thomas L. Eggerman, Eugenia Poliakov, T. Michael Redmond
Summary: Here, we provide evidence that LDLR plays a key role in the caveolae-mediated endocytosis pathway for SARS-CoV-2 virus internalization in ARPE-19 cells. Blocking ACE2 or cholesterol-rich lipid raft proteins did not prevent infection, while inhibition of cholesterol homeostasis using cyclodextrins and 25-HC reduced pseudovirion infection. Clathrin-dependent and flotillin-dependent rafts were not involved, but dynamin and caveolin-1 were found to be essential for virus entry. Furthermore, LDLR antibodies and siRNA-mediated knockdown of LDLR decreased pseudovirion infection. Therefore, we conclude that SARS-CoV-2 virus internalization in ARPE-19 cells primarily involves LDLR through a dynamin-dependent process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)