Review
Immunology
Yu Zhang, Xuefei Zhang, Hai-Qiang Dai, Hongli Hu, Frederick W. Alt
Summary: Cohesin-mediated chromatin loop extrusion plays a crucial role in the development and maturation of B cells, facilitating V(D)J recombination and class-switch recombination by presenting gene segments to RAG endonuclease. These processes are essential for immune responses.
NATURE REVIEWS IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Kefei Yu
Summary: This mini review discusses recent advances in understanding the function and regulation of AID in B cells, including its molecular structure, advances in high throughput techniques, and the mechanism of AID-mediated class switch recombination. These studies have provided insights into the biochemical properties and function of AID.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
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
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
Multidisciplinary Sciences
Rui-Xia Liu, Chuangyu Wen, Weibiao Ye, Yewei Li, Junxiong Chen, Qian Zhang, Weiqian Li, Wanfei Liang, Lili Wei, Jingdan Zhang, Ka-Wo Chan, Xueqin Wang, Xiangling Yang, Huanliang Liu
Summary: In this study, the altered clonotype, phenotype, and immunoglobulin subclasses of tumor-infiltrating B cells in colorectal cancer were identified. Remarkably, the changes in the B cell immunoglobulin signature could also be detected in the plasma of CRC patients, suggesting a distinct B cell response in CRC. The diagnostic model based on the altered plasma immunoglobulin signature showed improved sensitivity compared to traditional biomarkers, indicating its potential as a non-invasive method for CRC assessment.
Review
Cell Biology
Jing Zhao, Hui Peng, Jie Gao, Anna Nong, Haoming Hua, Shulin Yang, Liying Chen, Xiangsheng Wu, Hao Zhang, Juping Wang
Summary: This review focuses on the expression, functions, and mechanisms of tumor-derived immunoglobulins (Igs), comparing them with classical Igs produced by B lymphocytes and plasma cells. Future research directions, including structural characteristics, physicochemical properties, rearrangement and expression regulation mechanisms, signaling pathways, and clinical applications of tumor-derived Igs are also discussed.
CELL DEATH DISCOVERY
(2021)
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
Catherine Tang, Thomas MacCarthy
Summary: Activation-induced deaminase (AID) is an essential enzyme for antibody diversification through somatic hypermutation and class-switch recombination. G-quadruplex (G4) structures have been shown to form in the Ig switch regions, impacting the binding of AID. Computational predictions and biochemical validation reveal high G4 potential in specific human Ig heavy chain V (IGHV) genes, with potential mutability of certain hotspots and coldspots in the V region. These findings suggest functional G4s forming in the Ig V region.
FRONTIERS IN IMMUNOLOGY
(2021)
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)
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
Kris Covens, Bert Verbinnen, Britt G. de Jong, Leen Moens, Greet Wuyts, Geert Verheyen, Kris Nys, Jonathan Cremer, Stijn Smulders, Rik Schrijvers, Andreas Weinhaeusel, Severine Vermeire, Patrick Verschueren, Ellen De Langhe, Jacques J. M. van Dongen, Menno C. van Zelm, Xavier Bossuyt
Summary: Antibody-secreting cells are present in the peripheral blood of healthy individuals, and a small population of CD19+CD43+ B cells lacking CD27 expression has been characterized. These CD27-CD43+ cells exhibit similar characteristics to conventional plasmablasts but have differences in function and homing potential.
FRONTIERS IN IMMUNOLOGY
(2023)
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
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
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
Immunology
Justin H. M. Heltzel, Robert W. Maul, William Yang, Patricia J. Gearhart
Summary: This study demonstrates that the distance between the V region and J gene does not affect the extent of mutation. The majority of mutations occur within a 1 kb region downstream of the J gene, regardless of the specific J gene used. This suggests that mutations are targeted by AID interactions with RNA polymerase II.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Rajesh Ravindran, Jens Loebbermann, Helder I. Nakaya, Nooruddin Khan, Hualing Ma, Leonardo Gama, Deepa K. Machiah, Benton Lawson, Paul Hakimpour, Yi-chong Wang, Shuzhao Li, Prachi Sharma, Randal J. Kaufman, Jennifer Martinez, Bali Pulendran
Article
Multidisciplinary Sciences
Charles Sinclair, Gayathri Bommakanti, Luiz Gardinassi, Jens Loebbermann, Matthew Joseph Johnson, Paul Hakimpour, Thomas Hagan, Lydia Benitez, Andrei Todor, Deepa Machiah, Timothy Oriss, Anuradha Ray, Steven Bosinger, Rajesh Ravindran, Shuzhao Li, Bali Pulendran
Letter
Oncology
T. Zhang, J. K. Davidson-Moncada, P. Mukherjee, R. R. Furman, E. Bhavsar, Z. Chen, P. Hakimpour, N. Papavasiliou, W. Tam
BLOOD CANCER JOURNAL
(2017)
Article
Immunology
Grace Teng, Paul Hakimpour, Pablo Landgraf, Amanda Rice, Thomas Tuschl, Rafael Casellas, F. Nina Papavasiliou
Article
Immunology
Jason Z. Oh, Rajesh Ravindran, Benoit Chassaing, Frederic A. Carvalho, Mohan S. Maddur, Maureen Bower, Paul Hakimpour, Kiran P. Gill, Helder I. Nakaya, Felix Yarovinsky, R. Balfour Sartor, Andrew T. Gewirtz, Bali Pulendran
Article
Immunology
J Czarneski, P Berguer, P Bekinschtein, DC Kim, P Hakimpour, N Wagner, I Nepomnaschy, I Piazzon, SR Ross
EUROPEAN JOURNAL OF IMMUNOLOGY
(2002)