Article
Immunology
Emily Sible, Mary Attaway, Giuseppe Fiorica, Genesis Michel, Jayanta Chaudhuri, Bao Q. Vuong
Summary: This study reveals the critical role of ATM and MSH2 in regulating class-switch recombination (CSR) of immunoglobulins (Ig). ATM promotes this process through its interaction with APE1 via pS38-AID, and ATM and MSH2 cooperate to regulate nonhomologous end joining during CSR.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Immunology
Angelica W. Y. Lau, Vivian M. Turner, Katherine Bourne, Jana R. Hermes, Tyani D. Chan, Robert Brink
Summary: The BAFF/BAFFR signaling pathway is necessary for the generation of unmutated, GC-independent MBCs derived directly from activated B cells, while not affecting GC B cells or GC-derived MBCs. Both types of MBCs require input from this pathway for optimal long-term survival.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Estelle Vincendeau, Wenming Wei, Xuefei Zhang, Cyril Planchais, Wei Yu, Helene Lenden-Hasse, Thomas Cokelaer, Juliana Pipoli da Fonseca, Hugo Mouquet, David J. Adams, Frederick W. Alt, Stephen P. Jackson, Gabriel Balmus, Chloe Lescale, Ludovic Deriano
Summary: SHLD1 is a component of the Shieldin complex, playing a role in DNA repair via non-homologous end-joining (NHEJ), which is essential for lymphocyte development. However, it is dispensable for lymphocyte development and V(D)J recombination, but essential for class-switching recombination in activated B cells.
NATURE COMMUNICATIONS
(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
Marta Markiewicz-Potoczny, Anastasia Lobanova, Anisha M. Loeb, Oktay Kirak, Teresa Olbrich, Sergio Ruiz, Eros Lazzerini Denchi
Summary: The loss of TRF2 in mouse embryonic stem cells triggers a compensatory transcriptional program that renders TRF2 dispensable for cell survival and proliferation. The unique DNA damage response in TRF2-null ES cells is controlled by telomere-associated protein POT1B and chromatin remodelling factor BRD2, and is characterized by the upregulation of ZSCAN4.
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
Genetics & Heredity
Di Liu, Myron F. Goodman, Phuong Pham, Kefei Yu, Chih-Lin Hsieh, Michael R. Lieber
Summary: Activation-induced deaminase (AID) deaminates cytosine within single-stranded DNA. This study found that AID deamination on duplex DNA substrates is reduced when RNase A is added during transcription. The researchers also discovered that AID acts with similar efficiency on RNA-DNA fusion substrates and DNA-only substrates. Based on these findings, they proposed a model in which the mRNA tail plays a critical role in AID loading and collision with DNA strands.
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)
Article
Biochemistry & Molecular Biology
Anubhav Tamrakar, Prashant Kodgire
Summary: This study reveals the modulation of immune response by H. pylori outer membrane proteins in interaction with B-cells, providing insights into the pathogen's evasion strategies.
MOLECULAR IMMUNOLOGY
(2022)
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
Hongchang Zhao, Stella R. Hartono, Kirtney Mae Flores de Vera, Zheyuan Yu, Krishni Satchi, Tracy Zhao, Roger Sciammas, Lionel Sanz, Frederic Chedin, Jacqueline Barlow, Michela Di Virgilio
Summary: Class switch recombination is a crucial process for generating distinct antibody isotypes, and defects in this process are associated with autoimmune disorders and lymphoma genesis. In this study, we found that cells lacking two enzymes involved in removing R loops exhibited increased R loop formation and genome instability at the immunoglobulin heavy chain locus. However, this did not affect transcriptional activity, AID recruitment, or class switch recombination efficiency. Our findings suggest that senataxin and RNase H2 act together in removing R loops, promoting efficient repair and suppressing AID-dependent genome instability and insertional mutagenesis.
Article
Multidisciplinary Sciences
Arun Prakash Mishra, Suzanne A. Hartford, Sounak Sahu, Kimberly Klarmann, Rajani Kant Chittela, Kajal Biswas, Albert B. Jeon, Betty K. Martin, Sandra Burkett, Eileen Southon, Susan Reid, Mary E. Albaugh, Baktiar Karim, Lino Tessarollo, Jonathan R. Keller, Shyam K. Sharan
Summary: The presence of homologous chromosomes in close proximity to the DNA double strand breaks compensates for the defect in the interaction between tumor suppressor BRCA2 and DSS1, allowing for normal RAD51 recruitment during meiosis.
NATURE COMMUNICATIONS
(2022)
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
Yana P. Blokhina, Michelle A. Frees, An Nguyen, Masuda Sharifi, Daniel B. Chu, Kristi Bispo, Ivan Olaya, Bruce W. Draper, Sean M. Burgess
Summary: In zebrafish, the cohesin subunit Rad21l1 is essential for oogenesis but not necessary for spermatogenesis. Knocking out the rad21l1 gene results in female to male sex reversals and oocyte death, which can be partially prevented by deletion of the tp53 gene. This highlights the importance of a meiosis-specific cohesin subunit in oogenesis and its impact on female fertility.
Article
Biology
Jeongkwan Hong, Jae-Geun Lee, Kyung-Cheol Sohn, Kayoung Lee, Seoee Lee, Jinyoung Lee, Jihye Hong, Dongju Choi, Yeseul Hong, Hyo Sun Jin, Dae-Kyoung Choi, Su Ui Lee, Yun Kee, Jangham Jung, Young-Ki Bae, Ran Hee Hwang, Gang Min Hur, Jeong-Soo Lee, Hyunju Ro
Summary: Hong et al. have developed a new transgene expression system called IQ-Switch, which allows flexible regulation of gene expression in cell culture and zebrafish systems, avoiding issues caused by toxicity and gene silencing.
COMMUNICATIONS BIOLOGY
(2021)