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
Multidisciplinary Sciences
Liat Stoler-Barak, Ethan Harris, Ayelet Peres, Hadas Hezroni, Mirela Kuka, Pietro Di Lucia, Amalie Grenov, Neta Gurwicz, Meital Kupervaser, Bon Ham Yip, Matteo Iannacone, Gur Yaari, John D. Crispino, Ziv Shulman
Summary: The protein kinase DYRK1A is essential for B cell-mediated protection from viral infection and effective vaccination by regulating class switch recombination (CSR). It plays a crucial role in B cell immune responses, including attenuating B cell proliferation and promoting the production of pathogen-eliminating antibodies.
NATURE COMMUNICATIONS
(2023)
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
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
Biochemistry & Molecular Biology
Simin Zheng, Allysia J. Matthews, Numa Rahman, Kayleigh Herrick-Reynolds, Emily Sible, Jee Eun Choi, Alec Wishnie, Yan Kee Ng, Daniela Rhodes, Stephen J. Elledge, Bao Q. Vuong
Summary: Class switch recombination (CSR) is the process of B cells switching production from IgM/IgD to other immunoglobulin isotypes. SANBR, identified as a negative regulator of CSR, inhibits CSR through its BTB domain.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Abdul B. Hayran, Nina B. Liabakk, Per A. Aas, Anna Kusnierczyk, Cathrine B. Vagbo, Antonio Sarno, Tobias S. Iveland, Konika Chawla, Astrid Zahn, Javier M. Di Noia, Geir Slupphaug, Bodil Kavli
Summary: Activation-induced cytidine deaminase (AID) interacts with replication protein A (RPA) to promote conversion of cytosine to uracil in immunoglobulin (Ig) genes. Uracil-DNA glycosylase (UNG) plays a crucial role in Ig diversification and genome repair through its interaction with AID. The study shows that the UNG:RPA interaction is important for class switch recombination (CSR) and repair of AID-induced uracil, but has no significant impact on total genomic uracil levels.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Ahmed M. Refaat, Mikiyo Nakata, Afzal Husain, Hidetaka Kosako, Tasuku Honjo, Nasim A. Begum
Summary: B cells generate different classes of antibodies through class-switch recombination (CSR) mediated by classical non-homologous end joining (C-NHEJ). The RNA-binding protein HNRNPU promotes the joining of DNA breaks at the switch (S) regions through the 53BP1-shieldin DNA-repair complex. HNRNPU interacts with S region RNA/DNA G-quadruplexes and regulates R-loop and single-stranded DNA (ssDNA) accumulation. It facilitates CSR by forming and stabilizing the C-NHEJ ribonucleoprotein complex and preventing excessive R-loop accumulation, which can lead to genomic instability.
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.
Article
Biochemistry & Molecular Biology
Mitchell A. Ellison, Sanchirmaa Namjilsuren, Margaret K. Shirra, Matthew S. Blacksmith, Rachel A. Schusteff, Eleanor M. Kerr, Fei Fang, Yufei Xiang, Yi Shi, Karen M. Arndt
Summary: The Paf1 complex is a transcription elongation factor that regulates transcription efficiency and impacts RNA synthesis. The subunits Cdc73 and Rtf1 of Paf1C are important for the association with RNA polymerase II on active genes.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Shin-ichi Tsukumo, Poorani Ganesh Subramani, Noe Seija, Mizuho Tabata, Yoichi Maekawa, Yuya Mori, Chieko Ishifune, Yasushi Itoh, Mineto Ota, Keishi Fujio, Javier M. Di Noia, Koji Yasutomo
Summary: AFF3 directly regulates CSR by facilitating the recruitment of AID to the switch regions. Aff3 deficiency leads to decreased serum levels of immunoglobulins and weak resistance to Plasmodium yoelii infection in mice. An AFF3 risk allele for rheumatoid arthritis is associated with high expression of related genes in human B cells.
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
Cell Biology
Susie L. Brown, Jonathan J. Bauer, Juhyung Lee, Enatha Ntirandekura, Jason S. Stumhofer
Summary: Memory B cells (MBCs) play a crucial role in long-term immune response. This study identified two predominant MBC populations in response to P. yoelii infection, which are characterized by somatic hypermutation and expression of specific surface proteins. Further experiments showed that these MBC populations can produce antigen-specific antibodies and differentiate into B cells with a germinal center phenotype during secondary infection.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Genetics & Heredity
Emily Biernat, Mansi Verma, Chhabi K. Govind
Summary: RSC is an essential ATP-dependent chromatin remodeling complex in Saccharomyces cerevisiae. It regulates nucleosome-depleted regions (NDRs) by sliding flanking nucleosomes away from NDRs. Depletion of RSC leads to nucleosome encroachment in NDRs and transcription initiation defects. The study compared the effects of catalytic-dead Sth1 and rapid depletion of Sth1 on transcription. Rapid depletion of Sth1 reduces recruitment of TBP and Pol II, while the catalytic-dead mutant exhibits a severe reduction in TBP binding but accumulates Pol II in coding regions. The results suggest a role for RSC in transcription elongation and termination processes.
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
Tomokazu Yamaguchi, Takashi Suzuki, Teruki Sato, Akinori Takahashi, Hiroyuki Watanabe, Ayumi Kadowaki, Miyuki Natsui, Hideaki Inagaki, Satoko Arakawa, Shinji Nakaoka, Yukio Koizumi, Shinsuke Seki, Shungo Adachi, Akira Fukao, Toshinobu Fujiwara, Tohru Natsume, Akinori Kimura, Masaaki Komatsu, Shigeomi Shimizu, Hiroshi Ito, Yutaka Suzuki, Josef M. Penninger, Tadashi Yamamoto, Yumiko Imai, Keiji Kuba
Article
Biochemistry & Molecular Biology
Takeo K. Maeda, Daisuke Sugiura, Il-mi Okazaki, Takumi Maruhashi, Taku Okazaki
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Reina Mizuno, Takumi Maruhashi, Daisuke Sugiura, Kenji Shimizu, Mizuki Watada, Il-Mi Okazaki, Taku Okazaki
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2019)
Article
Multidisciplinary Sciences
Daisuke Sugiura, Takumi Maruhashi, Il-mi Okazaki, Kenji Shimizu, Takeo K. Maeda, Tatsuya Takemoto, Taku Okazaki
Article
Immunology
Hikari Okamura, Il-mi Okazaki, Kenji Shimizu, Takumi Maruhashi, Daisuke Sugiura, Reina Mizuno, Taku Okazaki
JOURNAL OF AUTOIMMUNITY
(2019)
Article
Biochemistry & Molecular Biology
Natsumi Maeda, Takumi Maruhashi, Daisuke Sugiura, Kenji Shimizu, II-mi Okazaki, Taku Okazaki
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Kenji Shimizu, Daisuke Sugiura, Il-mi Okazaki, Takumi Maruhashi, Yujiro Takegami, Chaoyang Cheng, Soichi Ozaki, Taku Okazaki
Review
Oncology
Takumi Maruhashi, Daisuke Sugiura, Il-mi Okazaki, Taku Okazaki
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2020)
Article
Multidisciplinary Sciences
Kenji Shimizu, Daisuke Sugiura, Il-mi Okazaki, Takumi Maruhashi, Tatsuya Takemoto, Taku Okazaki
Summary: PD-1 preferentially inhibits the expression of TCR-inducible genes when TCR:pMHC affinity is low, demonstrating a qualitative control of T cell responses by suppressing low-affinity T cells. Peptide-MHC affinities and MHC expression levels do not affect PD-1 sensitivity, suggesting that the strength of individual TCR signal is the key determinant of PD-1 sensitivity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Daisuke Sugiura, Il-mi Okazaki, Takeo K. Maeda, Takumi Maruhashi, Kenji Shimizu, Rieko Arakaki, Tatsuya Takemoto, Naozumi Ishimaru, Taku Okazaki
Summary: The study presents a method to enhance PD-1 function by targeting the PD-L1-CD80 duplex and demonstrates its effectiveness in alleviating symptoms of autoimmune diseases.
Article
Immunology
Takumi Maruhashi, Daisuke Sugiura, Il-Mi Okazaki, Kenji Shimizu, Takeo K. Maeda, Jun Ikubo, Harunori Yoshikawa, Katsumi Maenaka, Naozumi Ishimaru, Hidetaka Kosako, Tatsuya Takemoto, Taku Okazaki
Summary: The study identified stable pMHCII as a functional ligand of LAG-3 in both autoimmune and anti-cancer immunity, playing a crucial role in the suppressive activity of LAG-3.
Article
Multidisciplinary Sciences
Yosuke Mitani, Shinya Ohashi, Osamu Kikuchi, Yukie Nakai, Tomomi Ida, Ayaka Mizumoto, Yoshihiro Yamamoto, Tomoki Saito, Shigeki Kataoka, Junichi Matsubara, Atsushi Yamada, Masashi Kanai, Shigemi Matsumoto, Hiroaki Sakai, Kiyotsugu Yoshikawa, Eijiro Nakamura, Manabu Muto
Summary: Clinical cancer genome sequencing can detect potential targets for cancer treatment and variants of unknown significance. This study found that a HER2 mutation in colorectal cancer has oncogenic potential when accompanied by loss of APC function. The findings suggest that this HER2 mutation may be a potential therapeutic target for colorectal cancer.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Sana Inoue, Miki Imanishi, Ai Kanzaki, Atsumi Fujimoto, Marina Maeyama, Ayaka Okamoto, Hiroka Matsuda, Kiyotsugu Yoshikawa, Rei Takahashi
Summary: The role of cancer stem cells in apoptosis-resistant triple-negative breast cancer cells was investigated. The study revealed that these cells exhibit increased migration ability and up-regulated expression of transition-related genes.
ACTA HISTOCHEMICA ET CYTOCHEMICA
(2022)
Review
Immunology
Daisuke Sugiura, Kenji Shimizu, Takumi Maruhashi, Il-mi Okazaki, Taku Okazaki
Summary: PD-1 functions are strictly restricted during T-cell activation by the cis-interactions of PD-L1 and CD80, crucial for optimal T-cell responses. Sensitivity to PD-1 effects in T cells is essentially determined by intrinsic factors.
INTERNATIONAL IMMUNOLOGY
(2021)
Article
Immunology
Reina Mizuno, Daisuke Sugiura, Kenji Shimizu, Takumi Maruhashi, Mizuki Watada, Il-mi Okazaki, Taku Okazaki
FRONTIERS IN IMMUNOLOGY
(2019)