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
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
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)
Article
Immunology
Chloe Oudinet, Xuefei Zhang, Nadine Puget, Nia Kyritsis, Claire Leduc, Fatima-Zohra Braikia, Audrey Dauba, Frederick W. Alt, Ahmed Amine Khamlichi
Summary: Immunoglobulin class switch recombination plays a crucial role in humoral immune responses by altering the effector functions of antibodies. The A-NHEJ pathway in CSR shows a preference for longer junctional micro-homologies, and the molecular basis of S mu specificity remains unclear. Introducing the E mu enhancer into the S gamma 3 region confers the recombinational features of S mu to S gamma 3, indicating a bias for longer MH.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Michael Jonathan Lehrke, Michael Jeremy Shapiro, Matthew J. Rajcula, Madeleine M. Kennedy, Shaylene A. McCue, Kay L. Medina, Virginia Smith Shapiro
Summary: ABCB7 is essential for early B cell development, proliferation, and class switch recombination. Loss of ABCB7 results in replication-induced DNA damage and slowed DNA replication in pro-B cells.
Article
Multidisciplinary Sciences
Hai-Qiang Dai, Hongli Hu, Jiangman Lou, Adam Yongxin Ye, Zhaoqing Ba, Xuefei Zhang, Yiwen Zhang, Lijuan Zhao, Hye Suk Yoon, Aimee M. Chapdelaine-Williams, Nia Kyritsis, Huan Chen, Kerstin Johnson, Sherry Lin, Andrea Conte, Rafael Casellas, Cheng-Sheng Lee, Frederick W. Alt
Summary: RAG endonuclease initiates gene rearrangement in B cells by binding to specific DNA sequences and this process is influenced by chromatin structure. In progenitor B cells, locus contraction promotes gene rearrangement and loop extrusion also drives this process.
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
Immunology
Jana Koers, Casper Marsman, Juulke Steuten, Simon Tol, Ninotska I. L. Derksen, Anja ten Brinke, S. Marieke van Ham, Theo Rispens
Summary: In this study, the researchers used optimized in vitro culture conditions and in-depth assessment of B cell characteristics and signaling pathways to investigate the role of oxygen in regulating human naive B cell differentiation and class switch recombination. They found that normoxia promotes differentiation into functional antibody secreting cells, while a unique population of CD27(++) B cells is generated under hypoxia. Additionally, time-dependent transitions between hypoxic and normoxic oxygen levels during culture can direct different trajectories of human B cell differentiation and IgG class switch recombination.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Amy L. Kenter, Corey T. Watson, Jan-Hendrik Spille
Summary: During development, B and T lymphocytes generate diverse antigen receptors which allow organisms to respond to a wide range of pathogens. Studies suggest that genetic polymorphisms in the immunoglobulin heavy chain locus may influence immune-repertoire formation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Ellen D. Renner, Carolin E. Kraetz, Jordan S. Orange, Beate Hagl, Stacey Rylaarsdam, Gundula Notheis, Anne Durandy, Troy R. Torgerson, Hans D. Ochs
Summary: This study evaluated the correlation between B cell phenotype analysis and antigen responses in patients with CSRD, finding distinct patterns of antibody responses to a new antigen among different types of CSRD patients.
CLINICAL IMMUNOLOGY
(2021)
Article
Immunology
Pascal Irrgang, Juliane Gerling, Katharina Kocher, Dennis Lapuente, Philipp Steininger, Katharina Habenicht, Monika Wytopil, Stephanie Beileke, Simon Schaefer, Jahn Zhong, George Ssebyatika, Thomas Krey, Valeria Falcone, Christine Schuelein, Antonia Sophia Peter, Krystelle Nganou-Makamdop, Hartmut Hengel, Juergen Held, Christian Bogdan, Klaus Ueberla, Kilian Schober, Thomas H. Winkler, Matthias Tenbusch
Summary: RNA vaccines are effective in preventing SARS-CoV-2 infection, and high levels of neutralizing antibodies are crucial for vaccine-induced immunity. After the second mRNA vaccination, SARS-CoV-2-specific antibodies were increasingly composed of noninflammatory IgG4, which was further boosted by a third vaccination or breakthrough infections. This induction of IgG4 antibodies was not observed with adenoviral vectors. These findings have implications for the choice and timing of mRNA vaccine regimens, including booster shots.
SCIENCE IMMUNOLOGY
(2023)
Article
Cell Biology
Olga Mielczarek, Carolyn H. Rogers, Yinxiu Zhan, Louise S. Matheson, Michael J. T. Stubbington, Stefan Schoenfelder, Daniel J. Bolland, Biola M. Javierre, Steven W. Wingett, Csilla Varnai, Anne Segonds-Pichon, Simon J. Conn, Felix Krueger, Simon Andrews, Peter Fraser, Luca Giorgetti, Anne E. Corcoran
Summary: This study utilized tiled Capture Hi-C to map chromatin interactions within the Igh locus in progenitor B cells, revealing semi-rigid subdomains and flexible looping of VH genes. Deconvolution of single Igh locus conformations identified thousands of different structures, potentially contributing to the diversity of V(D)J recombination events. Additionally, all three immunoglobulin loci were found to participate in a specific network of interchromosomal interactions with genes encoding B cell-lineage factors, suggesting a model of interchromosomal coordination in B cell development.
Article
Multidisciplinary Sciences
Khalid H. Bhat, Saurabh Priyadarshi, Sarah Naiyer, Xinyan Qu, Hammad Farooq, Eden Kleiman, Jeffery Xu, Xue Lei, Jose F. Cantillo, Robert Wuerffel, Nicole Baumgarth, Jie Liang, Ann J. Feeney, Amy L. Kenter
Summary: Enhancers in the Igh locus play a major role in configuring locus architecture and V(D)J recombination. They are also linked to enhancer hub formation, locus contraction, and cohesin-mediated loop extrusion.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Yijang Xu, Hang Zhou, Ginell Post, Hong Zan, Paolo Casali
Summary: The study demonstrates that Rad52 mediates IgD CSR through a microhomology-based DNA repair pathway, leading to the expression of IgD in B cells.
NATURE COMMUNICATIONS
(2022)
Review
Immunology
Stelios Vlachiotis, Hassan Abolhassani
Summary: This article provides an overview of the tight regulation of B cells during the process of immunoglobulin class switch recombination (CSR) and its implications in immune-related clinical manifestations. Defects in CSR can contribute to various diseases.
EXPERT REVIEW OF CLINICAL IMMUNOLOGY
(2022)
Editorial Material
Immunology
Audrey Dauba, Fatima-Zohra Braikia, Chloe Oudinet, Ahmed Amine Khamlichi
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ashraf Al Madhoun, Sulaiman K. Marafie, Dania Haddad, Motasem Melhem, Mohamed Abu-Farha, Hamad Ali, Sardar Sindhu, Maher Atari, Fahd Al-Mulla
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Immunology
Florence Savigny, Corinne Schricke, Norinne Lacerda-Queiroz, Melanie Meda, Megane Nascimento, Sarah Huot-Marchand, Felipe Da Gama Monteiro, Bernhard Ryffel, Aurelie Gombault, Marc Le Bert, Isabelle Couillin, Nicolas Riteau
Summary: Research has found that STING deficiency exacerbates pulmonary fibrosis in IPF, and STING-mediated protection is associated with dysregulated neutrophils.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Ramzi Nehmar, Louis Fauconnier, Jose Alves-Filho, Dieudonnee Togbe, Aurore DeCauwer, Seiamak Bahram, Marc Le Bert, Bernhard Ryffel, Philippe Georgel
Summary: The study revealed the crucial role of AHR activation in the development of arthritis, while IL-22 deficiency aggravated arthritis symptoms. Activation of AHR can alleviate inflammation and reduce joint destruction, with a protective effect on type 3 innate lymphoid cells during acute arthritis.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Dania Haddad, Sumi Elsa John, Anwar Mohammad, Maha M. Hammad, Prashantha Hebbar, Arshad Channanath, Rasheeba Nizam, Sarah Al-Qabandi, Ashraf Al Madhoun, Abdullah Alshukry, Hamad Ali, Thangavel Alphonse Thanaraj, Fahd Al-Mulla
Summary: The study reveals significant differences in the spread and mutations of COVID-19 in different countries, with recombination mainly observed in North American and European sequences. Structural modeling suggests that the two most common mutations may enhance viral entry and replication capabilities.
Article
Multidisciplinary Sciences
Ashraf Al Madhoun, Dania Haddad, Mustafa Al Tarrah, Sindhu Jacob, Waleed Al-Ali, Rasheeba Nizam, Lavina Miranda, Fatema Al-Rashed, Sardar Sindhu, Rasheed Ahmad, Milad S. Bitar, Fahd Al-Mulla
Summary: The study investigated the regulatory mechanisms of CHOP expression in nonmetastatic and metastatic colorectal cancer cell lines treated with ONC201. Differences in signaling pathways affecting CHOP expression were observed, leading to varied cellular responses to ONC201 treatment. Further mechanistic studies are needed to validate these findings.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Ashraf Al Madhoun, Sardar Sindhu, Dania Haddad, Maher Atari, Rasheed Ahmad, Fahd Al-Mulla
Summary: Dental pulp stem cells have promising characteristics, but genotypic and phenotypic heterogeneities may impact their therapeutic potentials. Studies suggest that their heterogeneity arises from an interplay between intrinsic and extrinsic factors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Hematology
Meriem Taleb, Isabelle Maillet, Marc Le Bert, Catherine Mura
Summary: This study uncovers the critical role of autophagy in macrophages in regulating iron metabolism and systemic iron homeostasis. Autophagy deficiency results in iron overload by increasing ferroportin expression, impacting hepcidin expression, and influencing factors in duodenal enterocytes.
Article
Immunology
Sarah Huot-Marchand, Megane Nascimento, Elodie Culerier, Melissa Bourenane, Florence Savigny, Corinne Panek, Cindy Serdjebi, Marc Le Bert, Valerie F. J. Quesniaux, Bernhard Ryffel, Petr Broz, Nicolas Riteau, Aurelie Gombault, Isabelle Couillin
Summary: Chronic pulmonary inflammation and COPD are major health issues caused by air pollution and cigarette smoke exposure. Research has shown that NLRP3 and gasdermin D play important roles in CS-induced pulmonary inflammation and IL-1 beta release.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Ashraf Al Madhoun, Prashantha Hebbar, Rasheeba Nizam, Dania Haddad, Motasem Melhem, Mohamed Abu-Farha, Thangavel Alphonse Thanaraj, Fahd Al-Mulla
Summary: The study found an association between the CAV1 rs1997623 C/A variant and MetS in adult Arab individuals, while the association was weaker in Asian cohorts.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Flora Vasile, Elena Dossi, Julien Moulard, Pascal Ezan, Laure Lecoin, Martine Cohen-Salmon, Philippe Mailly, Marc Le Bert, Isabelle Couillin, Alexis Bemelmans, Nathalie Rouach
Summary: Activation of astroglial Pannexin 1 channels plays a crucial role in the inhibition of hippocampal neuronal networks through a negative feedback mechanism, by regulating purinergic signaling-mediated HCN-gated channels to decrease neuronal excitability.
Article
Cell Biology
Ashraf Al Madhoun, Dania Haddad, Rasheeba Nizam, Lavina Miranda, Shihab Kochumon, Reeby Thomas, Thangavel Alphonse Thanaraj, Rasheed Ahmad, Milad S. Bitar, Fahd Al-Mulla
Summary: The study identified an association between the CAV1 rs1997623 C > A variant and metabolic syndrome, with the A allele generating a transcriptionally active locus that enhances CAV1 expression through the binding of early B-cell factor 1 (EBF1). This is the first demonstration of EBF1's role in regulating CAV1 expression in individuals with the rs1997623 C > A variant through combined in vivo and in vitro experiments.
Article
Immunology
Sandra Carignon, Dorian De Moura Rodrigues, David Gosset, Elodie Culerier, Sarah Huot-Marchand, Florence Savigny, Eric Kaya, Valerie Quesniaux, Aurelie Gombault, Isabelle Couillin, Bernhard Ryffel, Marc Le Bert, Nicolas Riteau
Summary: The pathogenesis of chronic lung diseases involves recurrent micro-injuries of the epithelium, with a major role of surfactant-producing alveolar epithelial type 2 (AT2) cells. This study investigated the contribution of gas exchange-permissive alveolar epithelial type 1 (AT1) cells in inflammation and interstitial fibrosis, by depleting AT1 cells through repeated injury. The findings suggest that targeting AT1 cell depletion could be a novel approach for investigating chronic lung inflammatory diseases and identifying new therapeutic targets.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Urology & Nephrology
Delphine Sedda, Claire Mackowiak, Julie Pailloux, Elodie Culerier, Ana Dudas, Pauline Rontani, Nicolas Erard, Antoine Lefevre, Sylvie Mavel, Patrick Emond, Frederic Foucher, Marc Le Bert, Valerie F. J. Quesniaux, Michael J. Mihatsch, Bernhard Ryffel, Madeleine Erard-Garcia
Summary: Xanthinuria type II is a rare autosomal purine disorder that can lead to lethal obstructive nephropathy, highlighting the importance of early diagnosis and treatment.
Meeting Abstract
Immunology
Nicolas Riteau, Florence Savigny, Sandra Carignon, Sarah Huot Marchand, Eric Kaya, Bernhard Ryffel, Aurelie Gombault, Marc Le Bert, Isabelle Couillin
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)