Article
Genetics & Heredity
Sandrine Le Noir, Amelie Bonaud, Bastien Herve, Audrey Baylet, Francois Boyer, Sandrine Lecardeur, Zeliha Oruc, Christophe Sirac, Michel Cogne
Summary: The study investigates how DNA lesions inflicted by activation-induced deaminase (AID) differentially result in reshaping immunoglobulin genes in mature B-cells. It reveals that the 3'Regulatory Region (3'RR) plays a crucial role in promoting class switch recombination (CSR) at the IgH locus.
Article
Multidisciplinary Sciences
Xuefei Zhang, Hye Suk Yoon, Aimee M. Chapdelaine-Williams, Nia Kyritsis, Frederick W. Alt
Summary: This study reveals the critical role of 3' IgH CBEs in regulating gene transcription and joining during CSR processes, especially in focusing transcriptional activities on upstream C-H locus targets.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Genetics & Heredity
Rossella Cianci, Giorgio Mancino, Elena Galli, Eliseo Serone, Renato Massoud, Pietro D'Addabbo, Andrea Poscia, Alberto Borghetti, Ottavia Porzio, Riccardo Marmo, Giovanni Gambassi, Domenico Frezza
Summary: This study found that the concentrations of IgG subclasses decrease from IgG1 to IgG4 in both children and adults. The 3'RR1 enhancer hs1.2 alleles contribute to the control of IgG subclasses levels, but not IgE levels. This indicates that IgG and IgE are regulated by different mechanisms in humans.
Article
Immunology
Iman Dalloul, Brice Laffleur, Zeinab Dalloul, Batoul Wehbi, Florence Jouan, Baptiste Brauge, Paco Derouault, Jeanne Moreau, Sven Kracker, Alain Fischer, Anne Durandy, Sandrine Le Noir, Michel Cogne
Summary: AID is a key regulator of immunoglobulin gene diversification in B-cells, but recent research has shown that under certain conditions, the absence of AID can also lead to gene diversification. The repair process in these cases involves an increased usage of microhomology-mediated repair.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Audrey Dauba, Ahmed Amine Khamlichi
Summary: CSR is a crucial mechanism in adaptive immune responses, triggered by both T-cell-dependent and T-cell-independent antigens. Transcription of switch sequences and regulation within dynamic chromatin domains play key roles in controlling CSR.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Zsuzsanna Ortutay, Anna Gronholm, Melina Laitinen, Melinda Keresztes-Andrei, Ismail Hermelo, Marko Pesu
Summary: The proprotein convertase enzyme FURIN plays an important role in maintaining cellular homeostasis by promoting the proteolytic maturation of pro-proteins. In T cells, FURIN is crucial for maintaining immune tolerance and T helper cell polarization. A regulatory region upstream of the Furin gene was identified, and deletion of this region reduced the expression of Furin mRNA in activated mouse T cells and affected the expression of genes associated with IFN gamma regulation in Th1 type cells. The Furin genetic regulatory region specifically promoted IFN gamma secretion by activated T cells, indicating characteristics of a super-enhancer for Th1 cell fate.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Mattia Colucci, Elisabetta De Santis, Beatrice Totti, Mattia Miroballo, Francesco Tamiro, Giovanni Rossi, Ada Piepoli, Gabriella De Vincentis, Antonio Greco, Alessandra Mangia, Rossella Cianci, Lazzaro Di Mauro, Giuseppe Miscio, Vincenzo Giambra
Summary: This study analyzed antibody levels, antigen-specific B cells, and total T and NK cell subsets in subjects after BNT162b2 vaccination, finding significant increases in these components in former COVID-19 patients and highly responsive individuals. Additionally, genetic variants in the human immunoglobulin constant-gene locus were identified to be associated with response levels to the vaccine.
Article
Virology
Tami L. Coursey, Koenraad Van Doorslaer, Alison A. McBride
Summary: Persistent infection with oncogenic human papillomaviruses can lead to human cancers, with the viral genome replicating as a plasmid and being partitioned to daughter cells during cell division. Research suggests that the overall chromatin architecture of the region is crucial for efficient use of the replication origin.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Peter Symonds, Ana Marcu, Katherine W. Cook, Rachael L. Metheringham, Lindy G. Durrant, Victoria A. Brentville
Summary: This study demonstrates that tumors present citrullinated peptides that can stimulate Th1 and regulatory responses, and competition likely exists between peptides with similar affinities. Characterization of immune responses from epitopes identified by peptide elution is necessary to optimize peptide selection for tumor therapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Ryan S. MacLeod, Mark B. Meyer, Jinhu Xiong, Keisha M. Cawley, Yu Liu, Melda Onal, Nancy A. Benkusky, Jeff D. Thostenson, J. Wesley Pike, Charles A. O'Brien
Summary: RANKL is crucial for osteoclast formation and lymphocyte production. In mice, the region between -510 to -1413 does not significantly affect Tnfsf11 expression, bone mass, or lymphocyte production under normal physiological conditions.
Article
Immunology
Samantha Gokhale, Eton Victor, Jemmie Tsai, Eris Spirollari, Brygida Matracz, Shogo Takatsuka, Jaeyong Jung, Daisuke Kitamura, Ping Xie
Summary: In this study, the researchers found that the expression of IL-9 receptor (IL-9R) was significantly increased in mouse follicular B cells lacking TNFR-associated factor 3 (TRAF3), a critical regulator of B cell survival and function. They discovered a novel pathway in which TRAF3 suppresses B cell activation and Ig isotype switching by inhibiting IL-9R-JAK-STAT3 signaling. These findings provide new insights into understanding and treating human diseases involving abnormal B cell activation, such as autoimmune disorders.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Hematology
Yukiko Kimura, Eisaku Iwanaga, Kouta Iwanaga, Shinya Endo, Yoshitaka Inoue, Kenji Tokunaga, Yousuke Nagahata, Kyoko Masuda, Hiroshi Kawamoto, Masao Matsuoka
Summary: The study identified a conserved differentially methylated region (DMR) in the CEBPA 3'-untranslated region (UTR) that is associated with AML cases displaying a myeloid/NK/T-cell phenotype and downregulated CEBPA expression. This DMR was found to enhance transcription from the CEBPA native promoter and was found to have IKZF1-binding sites responsible for the increased transcription of CEBPA. These findings suggest that the CEBPA 3'-UTR DMR is a novel regulatory element involved in myeloid/NK/T-cell lineage leukemogenesis.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2021)
Article
Immunology
Florian Reizine, Mathieu Lesouhaitier, Murielle Gregoire, Kieran Pinceaux, Arnaud Gacouin, Adel Maamar, Benoit Painvin, Christophe Camus, Yves Le Tulzo, Pierre Tattevin, Matthieu Revest, Audrey Le Bot, Alice Ballerie, Berengere Cador-Rousseau, Mathieu Lederlin, Thomas Lebouvier, Yoann Launey, Maelle Latour, Clotilde Verdy, Delphine Rossille, Simon Le Gallou, Joelle Dulong, Caroline Moreau, Claude Bendavid, Mikael Roussel, Michel Cogne, Karin Tarte, Jean-Marc Tadie
Summary: The study revealed that ARDS patients with COVID-19 had increased MDSC and decreased CD8(pos) effector memory cell compared to patients with moderate COVID-19 pneumonia. The expansion of COVID-19-related MDSC was directly correlated to lymphopenia and enhanced arginase activity. T cell proliferative capacity in vitro was significantly reduced among COVID-19 patients but could be restored through arginine supplementation.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Review
Medicine, Research & Experimental
Virginie Pascal, Margaux Hiblot, Batoul Wehbi, Jean-Claude Aldigier, Michel Cogne
Summary: Mucosal immunity relies on a combination of natural and affinity maturated IgA to maintain a balance between tolerance and protective responses. Understanding the different types of humoral responses is crucial for developing strategies for immuno-intervention in mucosal vaccination and immunotherapy for chronic inflammatory bowel disease.
M S-MEDECINE SCIENCES
(2021)
Article
Allergy
Anne Marchalot, Catherine Horiot, Jean-Marie Lambert, Claire Carrion, Christelle Oblet, Justine Pollet, Michel Cogne, Jeanne Moreau, Brice Laffleur, Laurent Delpy
Summary: This study demonstrates the effectiveness of an antisense oligonucleotide (ASO) strategy in reducing IgE secretion and promoting allergen tolerance by inducing apoptosis of IgE1 antibody-secreting cells.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Urology & Nephrology
Vincent Javaugue, Virginie Pascal, Sebastien Bender, Sarah Nasraddine, Mathilde Dargelos, Mehdi Alizadeh, Alexis Saintamand, Matthieu Filloux, Paco Derouault, Sabrina Bouyer, Estelle Desport, Arnaud Jaccard, Frank Bridoux, Michel Cogne, Christophe Sirac
Summary: The study developed a high throughput sequencing assay to detect subtle clonal disorders in monoclonal gammopathy of renal significance, which could potentially improve the management of this kidney disease.
KIDNEY INTERNATIONAL
(2022)
Article
Multidisciplinary Sciences
Florian Reizine, Murielle Gregoire, Mathieu Lesouhaitier, Valentin Coirier, Juliette Gauthier, Celine Delaloy, Elise Dessauge, Florent Creusat, Fabrice Uhel, Arnaud Gacouin, Frederic Dessauge, Cecile Le Naoures, Caroline Moreau, Claude Bendavid, Yoann Daniel, Kilian Petitjean, Valerie Bordeau, Claire Lamaison, Caroline Piau, Vincent Cattoir, Mikael Roussel, Bernard Fromenty, Christian Michelet, Yves Le Tulzo, Jaroslaw Zmijewski, Ronan Thibault, Michel Cogne, Karin Tarte, Jean-Marc Tadie
Summary: Severe sepsis can lead to sustained immune dysfunction, resulting in organ failure, secondary infections, and late mortality. Supplementation with arginine or citrulline can restore T cell function and reduce immunosuppression induced by sepsis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Allergy
M. Cogne, Z. Dalloul, O. Deze, M. Le Goff, S. Thomas, M. Cahen, N. Ueda, B. Laffleur
Summary: Persisting adaptive humoral immunity relies on memory B lymphocytes and long-lived plasma cells. IgE responses, although protective against parasites and certain venoms, can have detrimental effects and result in chronic conditions with dramatic acute adverse events.
REVUE FRANCAISE D ALLERGOLOGIE
(2022)
Article
Immunology
Kathleen Santamaria, Fabienne Desmots, Simon Leonard, Gersende Caron, Marion Haas, Celine Delaloy, Fabrice Chatonnet, Delphine Rossille, Amandine Pignarre, Celine Monvoisin, Marine Seffals, Claire Lamaison, Michel Cogne, Karin Tarte, Thierry Fest
Summary: The expression of CD23 marker plays a crucial role in the differentiation of human LZ B-GC cells, as CD23 expression is restricted to the GC LZ. CD23-negative LZ B-GC cells can differentiate into plasmablasts, while cells expressing CD23 are unable to complete this differentiation process. Analysis indicates that the process of plasma cell differentiation involves a series of gene expression changes, including a transient MYC gene expression supporting B cell proliferation.
FRONTIERS IN IMMUNOLOGY
(2021)
Letter
Biochemistry & Molecular Biology
Diana Molino, Christine Durier, Anne Radenne, Corinne Desaint, Jacques Ropers, Soizic Courcier, Louis Victorien Vieillard, Claire Rekacewicz, Beatrice Parfait, Victor Appay, Frederic Batteux, Emmanuel Barillot, Michel Cogne, Behazine Combadiere, Christiane S. Eberhardt, Guy Gorochov, Philippe Hupe, Laetitia Ninove, Stephane Paul, Isabelle Pellegrin, Sylvie van der Werf, Maeva Lefebvre, Elisabeth Botelho-Nevers, Inmaculada Ortega-Perez, Marie Jaspard, Samba Sow, Jean Daniel Lelievre, Xavier de Lamballerie, Marie Paule Kieny, Eric Tartour, Odile Launay
Article
Immunology
Amelie Bos, Esil Aleyd, Lydia P. E. van der Steen, P. J. Winter, Niels Heemskerk, Stephan M. Pouw, Louis Boon, Rene J. P. Musters, Jantine E. Bakema, Cassian Sitaru, Michel Cogne, Marjolein van Egmond
Summary: IgA autoantibodies may play a role in autoimmune or chronic inflammatory diseases. A novel IgA autoimmune blistering model using genetically modified mice showed that IgA anti-collagen XVII could activate neutrophils and cause tissue damage, while treatment with anti-Fc alpha RI monoclonal antibodies prevented and resolved the disease.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Immunology
Michel Cogne, Thierry Fest, Said Aoufouchi
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Lina Zawil, Tiffany Marchiol, Baptiste Brauge, Alexis Saintamand, Claire Carrion, Elise Dessauge, Christelle Oblet, Sandrine Le Noir, Frederic Mourcin, Mylene Brousse, Paco Derouault, Mehdi Alizadeh, Yolla El Makhour, Celine Monvoisin, Julien Saint-Vanne, Simon Leonard, Stephanie Durand-Panteix, Karin Tarte, Michel Cogne
Summary: BCL2 is a commonly deregulated gene in various B-cell malignancies, and its deregulation may have different impacts on B-cell fate. This study designed two transgenic mouse models to compare the effects of BCL2 association with IgH3'RR and Ig kappa gene loci on B-cell fate and lymphoid tissues. The results showed that BCL2 association with IgH3'RR primarily impacted germinal center B-cell populations, while its association with Ig kappa locus primarily boosted the influx of plasma cells and the accumulation of long-lived plasma cells.
Review
Biochemistry & Molecular Biology
Ophelie Deze, Brice Laffleur, Michel Cogne
Summary: Mature B cells utilize class switch recombination (CSR) to diversify immunoglobulin (Ig) production, facilitated by activation-induced deaminase (AID) targeting cytosines in transcribed targeted S regions. G-rich sequences in S regions form canonical G-quadruplexes (G4s) DNA structures, favoring CSR. Small molecules interacting with G4-DNA (G4 ligands) can regulate CSR either positively or negatively. The specific regulatory role of G4 structures in CSR and lymphomagenesis remains a major issue in understanding immune responses.
Article
Immunology
Nicolas Denis-Lagache, Christelle Oblet, Tiffany Marchiol, Audrey Baylet, Ophelie Teteau, Iman Dalloul, Zeinab Dalloul, Lina Zawil, Ophelie Deze, Jeanne Cook-Moreau, Alexis Saintamand, Hend Boutouil, Ahmed Amine Khamlichi, Claire Carrion, Sophie Peron, Sandrine Le Noir, Brice Laffleur, Michel Cogne
Summary: This study investigates the deletion of a specific gene structure that is associated with antibody gene variation and class switching, using a new mouse model. The results suggest that this gene deletion is associated with an increase in self-reactive antibodies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Virginie Pascal, Marine Dupont, Paco de Rouault, David Rizzo, Delphine Rossille, Robin Jeannet, Thomas Daix, Bruno Francois, Steve Genebrier, Marie Cornic, Guillaume Monneret, Fabienne Venet, Juliette Ferrant, Mikael Roussel, Florian Reizine, Mathieu Le Souhaitier, Jean-Marc Tadie, Kartin Tarte, Jean Feuillard, Michel Cogne
Summary: To investigate the immune response architecture in COVID-19 patients and understand the factors that can cause or prevent ARDS, we analyzed the B cell responses using flow cytometry and Ig repertoire analysis. Flow cytometry with FlowSOM analysis revealed changes associated with COVID-19 inflammation, including an increase in double-negative B cells and ongoing plasma cell differentiation. We also found the expansion of two disconnected B cell repertoires. Analysis of Ig repertoire patterns showed an early expansion of IgG1 clonotypes with atypical CDR3 characteristics, which correlated with ARDS severity. Additionally, we observed a convergent response with progressively increasing somatic hypermutation and normal or short CDR3 in anti-SARS-CoV-2 clonotypes, which persisted until the memory B cell stage after recovery.
Article
Biochemistry & Molecular Biology
Ophelie Deze, Delfina Ordanoska, Delphine Rossille, Emma Miglierina, Brice Laffleur, Michel Cogne
Summary: Ig genes have the unique ability to be reshaped in B lymphocytes after encountering specific antigens, resulting in improved affinity and antibody production. Ig class switching, an important change in this process, is mediated by DNA repeats and DNA lesions. The discovery of IgH-like DNA repeats in the human IgH locus suggests their regulatory role in antibody production.