Article
Multidisciplinary Sciences
Fangzhu Zhao, Celina Keating, Gabriel Ozorowski, Namir Shaabani, Irene M. Francino-Urdaniz, Shawn Barman, Oliver Limbo, Alison Burns, Panpan Zhou, Michael J. Ricciardi, Jordan Woehl, Quoc Tran, Hannah L. Turner, Linghang Peng, Deli Huang, David Nemazee, Raiees Andrabi, Devin Sok, John R. Teijaro, Timothy A. Whitehead, Andrew B. Ward, Dennis R. Burton, Joseph G. Jardine
Summary: This study engineered three neutralizing antibodies with enhanced binding to the S protein of SARS-CoV-2 variants. The antibodies showed increased potency and breadth of neutralization against viral variants. Higher binding affinity was found to reduce the number of viral escape mutations. Studies in the Syrian hamster model demonstrated that affinity-matured antibodies provided superior protection compared to parental antibodies.
Article
Biochemistry & Molecular Biology
Qianwen Hu, Tingting Xu, Wenqian Zhang, Chuanxin Huang
Summary: The transcription factor Bach2 plays a crucial role in regulating the germinal center (GC) reaction and is involved in the survival and maintenance of GC B cells and memory B cell formation. Bach2 controls GC programs by repressing pro-apoptotic gene Bim and genes related to cell stress response and metabolic processes.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Immunology
Domenick E. Kennedy, Marcus R. Clark
Summary: Recent advancements have shed new light on the coordinated development of high affinity antibody responses through germinal centers (GCs), highlighting the importance of distinct cell states in GC B cell function, selection, proliferation, and somatic hypermutation (SHM). This new model presents opportunities for understanding the evolution of immunity in infectious, autoimmune, and neoplastic diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Jingwei Wang, Tianbao Li, Hong Zan, Carlos E. Rivera, Hui Yan, Zhenming Xu
Summary: The study showed that LUBAC controls cFLIP expression, inhibits the effects of caspase 8 and IL-21-activated caspase 9, thereby suppressing apoptosis of CD40 and IL-21-activated B cells, promoting GC B cell survival.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Haripriya Vaidehi Narayanan, Alexander Hoffmann
Summary: Antibody-mediated adaptive immunity must provide long-term protection against rapidly mutating pathogens in a diverse human population. Understanding the multiscale germinal center (GC) reaction, which is responsible for the evolution of high-affinity antigen-specific antibodies, is crucial. This article advocates for a mechanistic understanding of B-cell dynamics at organism, tissue/cellular, and molecular scales, and emphasizes the importance of quantitative multi-scale mathematical models in predicting B-cell and GC reaction dynamics for practical applications such as vaccine design.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Bonnie Huang, James D. Phelan, Silvia Preite, Julio Gomez-Rodriguez, Kristoffer H. Johansen, Hirofumi Shibata, Arthur L. Shaffer, Qin Xu, Brendan Jeffrey, Martha Kirby, Stacie Anderson, Yandan Yang, Selamawit Gossa, Dorian B. McGavern, Louis M. Staudt, Pamela L. Schwartzberg
Summary: In this study, the researchers used a CRISPR screen to identify the role of HIF-1 alpha in regulating Tfh cell development. They also discovered multiple components and mechanisms involved in the regulation of Tfh and Th1 cell differentiation.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Nimitha R. Mathew, Jayalal K. Jayanthan, Ilya Smirnov, Jonathan L. Robinson, Hannes Axelsson, Sravya S. Nakka, Aikaterini Emmanouilidi, Paulo Czarnewski, William T. Yewdell, Karin Schon, Cristina Lebrero-Fernandez, Valentina Bernasconi, William Rodin, Ali M. Harandi, Nils Lycke, Nicholas Borcherding, Jonathan W. Yewdell, Victor Greiff, Mats Bemark, Davide Angeletti
Summary: The study identified differences in antigen-specific B cell responses in lymphoid organs, spleen, and lungs after infection, as well as germinal center B cell subpopulations in different organs. Transcriptional differences were found between memory cells in lungs and lymphoid organs, and organ-restricted clonal expansion was observed. Furthermore, significant clonal overlap between germinal center-derived memory and plasma cells was discovered.
Article
Immunology
Alessia Corrado, Richard P. Ramonell, Matthew C. Woodruff, Christopher Tipton, Sarah Wise, Joshua Levy, John DelGaudio, Merin E. Kuruvilla, Kelly R. Magliocca, Deepak Tomar, Swetha Garimalla, Christopher D. Scharer, Jeremy M. Boss, Hao Wu, Sanjeev Gumber, Chris Fucile, Greg Gibson, Alexander Rosenberg, Inaki Sanz, F. Eun-Hyung Lee
Summary: This study describes a novel mechanism of GC-independent, extrafollicular IgE ASC formation at the nasal mucosa, where activated IgD+ naive B cells locally undergo direct and indirect IgE class switch.
MUCOSAL IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Dessislava Malinova, Laabiah Wasim, Rebecca Newman, Ana Martinez-Riano, Niklas Engels, Pavel Tolar
Summary: The research identified the crucial role of B-cell endosomal trafficking pathways in regulating antigen uptake, B-cell proliferation, and antibody responses, especially in germinal center B-cell reactions and high-affinity antibody production.
Review
Immunology
Clara Young, Angelica W. Y. Lau, Deborah L. Burnett
Summary: Germinal centers play a crucial role in balancing self-tolerance and foreign binding, with the outcomes depending on factors such as affinity and avidity. If self-reactive B cells cannot be repaired through mutation, self-tolerance prevails and restricts the antibody response to the foreign pathogen.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Mathematical & Computational Biology
Zishuo Yan, Hai Qi, Yueheng Lan
Summary: A model is established to investigate the self-organizing process of the germinal center (GC) and reveals the crucial role of the development of dark and light zones in maintaining effective competition and promoting affinity maturation. The study discovers a phase transition that determines the critical GC volume for successful growth.
MATHEMATICAL BIOSCIENCES AND ENGINEERING
(2022)
Article
Cell Biology
Cecilia B. Cavazzoni, Benjamin L. Hanson, Manuel A. Podesta, Elsa D. Bechu, Rachel L. Clement, Hengcheng Zhang, Joe Daccache, Tamara Reyes-Robles, Erik C. Hett, Kalpit A. Vora, Olugbeminiyi O. Fadeyi, Rob C. Oslund, Daria J. Hazuda, Peter T. Sage
Summary: This study reveals the roles of follicular helper T cells (Tfh cells) and follicular regulatory T cells (Tfr cells) in the germinal center (GC) reactions after SARS-CoV-2 spike protein vaccination. Tfh cells promote the frequency and somatic hypermutation (SHM) of Spike-specific GC B cells, while Tfr cells control SHM and clonal diversity in the GC by limiting clonal competition.
Article
Immunology
Yutaro Yada, Masanori Matsumoto, Takeshi Inoue, Akemi Baba, Ryota Higuchi, Chie Kawai, Masashi Yanagisawa, Daisuke Kitamura, Shouichi Ohga, Tomohiro Kurosaki, Yoshihiro Baba
Summary: STIM-mediated survival signals play a crucial role in the selection and maintenance of GC B cells by regulating apoptosis and high-affinity B cell generation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Immunology
Zhian Chen, Yanfang Cui, Yin Yao, Bo Liu, Joseph Yunis, Xin Gao, Naiqi Wang, Pablo F. Canete, Zewen Kelvin Tuong, Hongjian Sun, Hao Wang, Siling Yang, Runli Wang, Yew Ann Leong, David Simon Davis, Jiahuan Qin, Kaili Liang, Jun Deng, Conan K. Wang, Yen-Hua Huang, Jonathan A. Roco, Sam Nettelfield, Huaming Zhu, Huajun Xu, Zhijia Yu, David Craik, Zheng Liu, Hai Qi, Christopher Parish, Di Yu
Summary: In antibody responses, mutated germinal center B (BGc) cells are positively selected for reentry or differentiation, with the support of TFH cell-derived signals including CD40 and IL-21. The binding and signaling of IL-21 in BGc cells is reduced compared to non-BGc cells, due to low cellular heparan sulfate (HS) sulfation. Ndst1-mediated N-sulfation of HS in B cells promotes IL-21 binding and signal strength, and selective desensitization to IL-21 occurs in BGc cells. Therefore, the biochemical regulation of IL-21 availability and signal strength plays a crucial role in GC selection.
SCIENCE IMMUNOLOGY
(2023)
Article
Cell Biology
Leerang Yang, Matthew Van Beek, Zijun Wang, Frauke Muecksch, Marie Canis, Theodora Hatziioannou, Paul D. Bieniasz, Michel C. Nussenzweig, Arup K. Chakraborty
Summary: The Omicron variant is resistant to neutralization by most antibodies produced from two doses of mRNA vaccines, but a third dose enhances the production of anti-Omicron neutralizing antibodies. Through computational modeling and data from vaccinated individuals, we have identified the mechanisms behind this observation. Limited antigen availability after the first dose leads to a dominant B cell response targeting immunodominant epitopes that are mutated in the Omicron-like variant. The second dose expands memory cells that produce ineffective antibodies for such variants, but also facilitates antigen transport and masking of antigenic sites, resulting in the generation of memory B cells targeting less mutated subdominant epitopes in Omicron. The third dose further expands these cells and boosts the production of neutralizing antibodies against the variant.
Article
Gastroenterology & Hepatology
Jieliang Chen, Yaming Li, Fritz Lai, Yang Wang, Kathrin Sutter, Ulf Dittmer, Jianyu Ye, Wenjing Zai, Min Liu, Fang Shen, Min Wu, Kongying Hu, Baocun Li, Mengji Lu, Xiaonan Zhang, Jiming Zhang, Jianhua Li, Qingfeng Chen, Zhenghong Yuan
Summary: The study identified IFN-alpha 14 as the most effective subtype in suppressing HBV replication, with significantly lower concentration values compared to conventional IFN-alpha 2. IFN-alpha 14 triggered a strong antiviral response through IFN-alpha and IFN-gamma signaling crosstalk, revealing mechanisms for potent HBV suppression. The findings deepen the understanding of the diverse activities of IFN-alpha subtypes and the synergistic effects of IFN-alpha and IFN-gamma signaling, potentially leading to improved HBV therapy strategies.
Article
Immunology
Xinyi Qi, Jinxin Qiu, Jiali Chang, Yan Ji, Qi Yang, Guoliang Cui, Liming Sun, Qian Chai, Jun Qin, Ju Qiu
Summary: Brg1 plays a critical role in the differentiation of NKp46(+) ILC3s by promoting T-bet expression in NKp46(-) ILC3s, facilitating the conversion of NKp46(-) ILC3s into NKp46(+) ILC3s, and ultimately restraining intestinal inflammation. Our study demonstrates that Brg1 enhances T-bet and inhibits GM-CSF expression in ILC3s through a cell-intrinsic manner, highlighting its essential role in regulating intestinal immunity.
MUCOSAL IMMUNOLOGY
(2021)
Article
Oncology
Qiuli Liu, Jian Pang, Lin-ang Wang, Zhuowei Huang, Jing Xu, Xingxia Yang, Qiubo Xie, Yiqiang Huang, Tang Tang, Dali Tong, Gaolei Liu, Luofu Wang, Dianzheng Zhang, Qiang Ma, Hualiang Xiao, Weihua Lan, Jun Qin, Jun Jiang
Summary: The study demonstrates that PHF8 is essential for the development of NEPC by transcriptionally upregulating the FOXA2 gene, which regulates the expression of genes involved in NEPC development. Both PHF8 and FOXA2 could potentially serve as biomarkers for NEPC and targeting them may be a therapeutic strategy for NEPC treatment.
JOURNAL OF PATHOLOGY
(2021)
Article
Cell Biology
Qiqi Cao, Chun Zhao, Congjing Wang, Lingbo Cai, Meng Xia, Xiaolan Zhang, Jian Han, Yangyang Xu, Junqiang Zhang, Xiufeng Ling, Xiang Ma, Ran Huo
Summary: Mutations in PATL2, such as PATL2(Y217N), disrupt oocyte maturation by reducing ubiquitination levels and affecting translational regulation of Mos mRNA, leading to impaired MAPK signaling pathway and meiosis in oocytes. This highlights a new mechanism of action for PATL2 in maternal mRNA translation regulation during oocyte meiotic maturation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Qiang Pan, Shanshan Zhong, Hanling Wang, Xuege Wang, Ni Li, Yaqi Li, Guoying Zhang, Huairui Yuan, Yannan Lian, Qilong Chen, Ying Han, Jiacheng Guo, Qiuli Liu, Tong Qiu, Jun Jiang, Qintong Li, Minjia Tan, Huiyong Yin, Junjie Peng, Yichuan Xiao, Jun Qin
Summary: Cholesterol metabolism is closely related to colorectal cancer, but the clinical benefit of statins in inhibiting the mevalonate pathway is uncertain. This study reveals that ZMYND8 plays a crucial role in enhancing de novo cholesterol biosynthesis and promoting the growth of intestinal tumors with high YAP expression.
Article
Cell Biology
Cheng Wang, Hong Lv, Xiufeng Ling, Hong Li, Feiyang Diao, Juncheng Dai, Jiangbo Du, Ting Chen, Qi Xi, Yang Zhao, Kun Zhou, Bo Xu, Xiumei Han, Xiaoyu Liu, Meijuan Peng, Congcong Chen, Shiyao Tao, Lei Huang, Cong Liu, Mingyang Wen, Yangqian Jiang, Tao Jiang, Chuncheng Lu, Wei Wu, Di Wu, Minjian Chen, Yuan Lin, Xuejiang Guo, Ran Huo, Jiayin Liu, Hongxia Ma, Guangfu Jin, Yankai Xia, Jiahao Sha, Hongbing Shen, Zhibin Hu
Summary: Children conceived through assisted reproductive technology (ART) carry more germline de novo mutations (gDNMs) than spontaneously conceived children, primarily originating from fathers. Infertility of the father is associated with elevated paternal DNMs in ART offspring, while the use of specific drugs triggers an increase in maternal DNMs. Therefore, evaluating the germline status of fathers in ART families is crucial.
Article
Developmental Biology
Shuai Zhou, Yueshuai Guo, Haifeng Sun, Lu Liu, Liping Yao, Chao Liu, Yuanlin He, Shanren Cao, Cheng Zhou, Mingrui Li, Yumeng Cao, Congjing Wang, Qianneng Lu, Wei Li, Xuejiang Guo, Ran Huo
Summary: The study reveals that maternal RNF114 plays a crucial role in degrading important substrates during the maternal-to-zygotic transition, regulating the activation of major ZGA in mouse embryos. Misregulation of this process may impede appropriate ZGA activation.
Article
Obstetrics & Gynecology
Qianneng Lu, Xiaolan Zhang, Qiqi Cao, Congjing Wang, Jie Ding, Chun Zhao, Junqiang Zhang, Xiufeng Ling, Qingxia Meng, Ran Huo, Hong Li
Summary: In this study, five heterozygous variants of the TUBB8 gene were identified in infertile patients, with two of the variants confirmed to be associated with infertility phenotypes through in vitro experiments. The results expand the range of TUBB8 variants and phenotypic spectrum related to female infertility.
REPRODUCTIVE SCIENCES
(2021)
Article
Cell Biology
Mingrui Li, Chao Ren, Shuai Zhou, Yuanlin He, Yueshuai Guo, Hao Zhang, Lu Liu, Qiqi Cao, Congjing Wang, Jie Huang, Yue Hu, Xue Bai, Xuejiang Guo, Wenjie Shu, Ran Huo
Summary: The study found that abnormal expression of splicing regulation proteins in aged oocytes affects the splicing of DNA repair-related genes in 2-cell embryos, reducing their developmental potential.
Article
Obstetrics & Gynecology
Lu Liu, Jie Huang, Anlan He, Shuai Zhou, Qianneng Lu, Xiaoning Yu, Xue Bai, Mingrui Li, Ran Huo
Summary: This study found that 4,4'-dimethoxychalcone (DMC) can improve the quality of postovulatory ageing (POA) oocytes by eliminating accumulated reactive oxygen species (ROS), reducing apoptosis, improving mitochondrial distribution, and restoring the actin cap formation. DMC supplementation activates autophagy to protect oocytes from the effects of POA, leading to improved fertilization and developmental potential.
REPRODUCTIVE BIOMEDICINE ONLINE
(2022)
Article
Immunology
Zhong Fang, Yi Zhang, Zhaoqin Zhu, Cong Wang, Yao Hu, Xiuhua Peng, Dandan Zhang, Jun Zhao, Bisheng Shi, Zhongliang Shen, Min Wu, Chunhua Xu, Jieliang Chen, Xiaohui Zhou, Youhua Xie, Hui Yu, Xiaonan Zhang, Jianhua Li, Yunwen Hu, Maya Kozlowski, Antonio Bertoletti, Zhenghong Yuan
Summary: HBV exposure in children usually leads to chronic infection and the detection of HBsAg-specific CD8(+) T cells is rare. This study found that mMDSCs migrate to the thymus and eliminate HBsAg-specific CD8(+) thymocytes, resulting in specific tolerance to HBV.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Qiaofang Chu, Jianhua Li, Jieliang Chen, Zhenghong Yuan
Summary: Hepatitis B virus (HBV) changes miRNA packaging into extracellular vesicles (EVs) to facilitate its replication, and the EV miRNAs are associated with antiviral function, revealing a novel mechanism for HBV replication.
JOURNAL OF GENERAL VIROLOGY
(2022)
Article
Immunology
Yuye Yin, Xinyi Yang, Shusheng Wu, Xinyu Ding, Huamin Zhu, Xuehui Long, Yuliang Wang, Sulan Zhai, Yun Chen, Nan Che, Jingjing Chen, Xiaoming Wang
Summary: This study reveals the critical role of Jmjd1c in regulating plasma cell differentiation and rheumatoid arthritis (RA) in B cells. Jmjd1c demethylates STAT3, maintains its normal activity, and restrains plasma cell generation.
Article
Biochemistry & Molecular Biology
Cheng Wang, Yayun Gu, Jun Zhou, Jie Zang, Xiufeng Ling, Hong Li, Lingmin Hu, Bei Xu, Bo Zhang, Na Qin, Hong Lv, Weiwei Duan, Yue Jiang, Yuanlin He, Tao Jiang, Congcong Chen, Xiumei Han, Kun Zhou, Bo Xu, Xiaoyu Liu, Shiyao Tao, Yangqian Jiang, Jiangbo Du, Juncheng Dai, Feiyang Diao, Chuncheng Lu, Xuejiang Guo, Ran Huo, Jiayin Liu, Yuan Lin, Yankai Xia, Guangfu Jin, Hongxia Ma, Hongbing Shen, Zhibin Hu
Summary: This study investigates the association between assisted reproductive technology (ART) and initial leukocyte telomere length (LTL) using whole-genome sequencing (WGS) data. The study finds that one-year-old children conceived by ART have shorter LTLs, especially in those conceived through blastocyst-stage embryo transfer. Mouse experiments also confirm that blastocyst-stage embryo transfer results in shorter telomere lengths.
Article
Immunology
Le Zhang, Xuehui Long, Yuye Yin, Jun Wang, Huamin Zhu, Jingjing Chen, Yuliang Wang, Yun Chen, Xiaoming Wang
Summary: Regulatory T cells play important roles in maintaining immune homeostasis and immune tolerance during pregnancy. This study revealed the critical role of H3K36me2 methyltransferase Nsd2 in Treg recruitment at the maternal-fetal interface. Loss of Nsd2 disrupted maternal-fetal immune tolerance, leading to severe fetal loss.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)