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
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
Immunology
Juhee Pae, Jonatan Ersching, Tiago B. R. Castro, Marta Schips, Luka Mesin, Samuel J. Allon, Jose Ordovas-Montanes, Coraline Mlynarczyk, Ari Melnick, Alejo Efeyan, Alex K. Shalek, Michael Meyer-Hermann, Gabriel D. Victora
Summary: During affinity maturation, GC B cells undergo proliferation and hypermutation in the dark zone, followed by selection in the light zone. Cyclin D3 plays a crucial role in controlling the anatomical segregation and cell cycle of GC B cells, and a specific mutation can lead to clonal B cell lymphoproliferation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
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
Cell Biology
Gaetano D'Amato, Ragini Phansalkar, Jeffrey A. Naftaly, Xiaochen Fan, Zhainib A. Amir, Pamela E. Rios Coronado, Dale O. Cowley, Kelsey E. Quinn, Bikram Sharma, Kathleen M. Caron, Alessandra Vigilante, Kristy Red-Horse
Summary: Endocardial cells have the potential to differentiate into coronary endothelial cells and regenerate blood vessels lost during cardiac injury. This study used mouse genetics and scRNA-seq to identify the molecular mechanisms involved in endocardial angiogenesis. It was found that CXCL12/CXCR4 signaling is specifically required for artery morphogenesis, and a transitioning population expressing Bmp2 was identified as important during mid-gestation.
DEVELOPMENTAL CELL
(2022)
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)
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)
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
Immunology
Doaa Waly, Aradana Muthupandian, Chia-Wei Fan, Harrison Anzinger, Brad G. G. Magor
Summary: This study reveals the existence of Aicda(+) cell clusters in fish that functionally resemble germinal centers in mammals. These clusters undergo B-cell clonal expansion and VDJ somatic hypermutation to achieve antibody affinity maturation. The study also provides evidence for positive selection for replacement mutations in regions encoding the antigen contact loops, leading to functional antibody modification. Additionally, melano-macrophages in the clusters trap antigens used for post-mutation B-cell selection, serving a role similar to follicular dendritic cells in mammalian germinal centers.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Adam J. Fike, Sathi Babu Chodisetti, Nathaniel E. Wright, Kristen N. Bricker, Phillip P. Domeier, Mark Maienschein-Cline, Aaron M. Rosenfeld, Sara A. Luckenbill, Julia L. Weber, Nicholas M. Choi, Eline T. Luning Prak, Malay Mandal, Marcus R. Clark, Ziaur S. M. Rahman
Summary: This study reveals the important role of signal transducer and activator of transcription 3 (STAT3) in germinal centers (GCs). STAT3 deficiency alters GC structure, reducing the development of long-lived plasma cells (LL-PCs) but increasing the number of memory B cells (MBCs). STAT3 regulates GC B cell recycling, maintaining GC zone organization and controlling GC egress of plasma cells while negatively regulating MBC output.
Article
Immunology
Yavuz F. Yazicioglu, Eros Marin, Ciaran Sandhu, Silvia Galiani, Iwan G. A. Raza, Mohammad Ali, Barbara Kronsteiner, Ewoud B. Compeer, Moustafa Attar, Susanna J. Dunachie, Michael L. Dustin, Alexander J. Clarke
Summary: Clarke and colleagues discovered that germinal center B cells have dynamic mitochondria regulated by the transcription factor TFAM. TFAM helps the B cells enter the germinal center reaction by modulating cellular motility. Understanding this mechanism is important as germinal center B cells undergo rapid proliferation in a hypoxic microenvironment.
Article
Immunology
Haley L. Dugan, Christopher T. Stamper, Lei Li, Siriruk Changrob, Nicholas W. Asby, Peter J. Halfmann, Nai-Ying Zheng, Min Huang, Dustin G. Shaw, Mari S. Cobb, Steven A. Erickson, Jenna J. Guthmiller, Olivia Stovicek, Jiaolong Wang, Emma S. Winkler, Maria Lucia Madariaga, Kumaran Shanmugarajah, Maud O. Jansen, Fatima Amanat, Isabelle Stewart, Henry A. Utset, Jun Huang, Christopher A. Nelson, Ya-Nan Dai, Paige D. Hall, Robert P. Jedrzejczak, Andrzej Joachimiak, Florian Krammer, Michael S. Diamond, Daved H. Fremont, Yoshihiro Kawaoka, Patrick C. Wilson
Summary: Analyzing the evolution of memory B cells (MBCs) against SARS-CoV-2 is crucial for understanding antibody recall upon secondary exposure. Single-cell sequencing was used to profile SARS-CoV-2-reactive B cells in COVID-19 patients, revealing enrichment of SARS-CoV-2 spike-specific cells in the memory compartment and highly mutated variable genes in endemic HCoV-reactive antibody-secreting cells. Additionally, MBCs exhibited pronounced maturation to NP and ORF8 over time.
Review
Immunology
Clara Young, Robert Brink
Summary: Germinal center B cells play a crucial role in producing high-affinity antibodies essential for protective immunity. Recent advancements in single cell and gene editing technologies have shed new light on the complex processes involved in GC B cell biology. Understanding the replication, death, retention, and differentiation of high-affinity and class-switched B cells in the GC is key to improving vaccine effectiveness and overcoming current challenges in the field.
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
Tom S. Weber, Mark Dukes, Denise C. Miles, Stefan P. Glaser, Shalin H. Naik, Ken R. Duffy
BMC SYSTEMS BIOLOGY
(2016)
Article
Biology
Tom S. Weber, Leila Perie, Ken R. Duffy
JOURNAL OF MATHEMATICAL BIOLOGY
(2016)
Article
Cell & Tissue Engineering
Delfim Duarte, Edwin D. Hawkins, Olufolake Akinduro, Heather Ang, Katia De Filippo, Isabella Y. Kong, Myriam Haltalli, Nicola Ruivo, Lenny Straszkowski, Stephin J. Vervoort, Catriona McLean, Tom S. Weber, Reema Khorshed, Chiara Pirillo, Andrew Wei, Saravana K. Ramasamy, Anjali P. Kusumbe, Ken Duffy, Ralf H. Adams, Louise E. Purton, Leo M. Carlin, Cristina Lo Celso
Article
Multidisciplinary Sciences
O. Akinduro, T. S. Weber, H. Ang, M. L. R. Haltalli, N. Ruivo, D. Duarte, N. M. Rashidi, E. D. Hawkins, K. R. Duffy, C. Lo Celso
NATURE COMMUNICATIONS
(2018)
Article
Multidisciplinary Sciences
D. Merino, T. S. Weber, A. Serrano, F. Vaillant, K. Liu, B. Pal, L. Di Stefano, J. Schreuder, D. Lin, Y. Chen, M. L. Asselin-Labat, T. N. Schumacher, D. Cameron, G. K. Smyth, A. T. Papenfuss, G. J. Lindeman, J. E. Visvader, S. H. Naik
NATURE COMMUNICATIONS
(2019)
Article
Biology
Gianfelice Meli, Tom S. Weber, Ken R. Duffy
JOURNAL OF MATHEMATICAL BIOLOGY
(2019)
Article
Biochemical Research Methods
Luyi Tian, Xueyi Dong, Saskia Freytag, Kim-Anh Le Cao, Shian Su, Abolfazl JalalAbadi, Daniela Amann-Zalcenstein, Tom S. Weber, Azadeh Seidi, Jafar S. Jabbari, Shalin H. Naik, Matthew E. Ritchie
Correction
Multidisciplinary Sciences
D. Merino, T. S. Weber, A. Serrano, F. Vaillant, K. Liu, B. Pal, L. Di Stefano, J. Schreuder, D. Lin, Y. Chen, M. L. Asselin-Labat, T. N. Schumacher, D. Cameron, G. K. Smyth, A. T. Papenfuss, G. J. Lindeman, J. E. Visvader, S. H. Naik
NATURE COMMUNICATIONS
(2019)
Article
Cell Biology
Dawn S. Lin, Luyi Tian, Sara Tomei, Daniela Amann-Zalcenstein, Tracey M. Baldwin, Tom S. Weber, Jaring Schreuder, Olivia J. Stonehouse, Jai Rautela, Nicholas D. Huntington, Samir Taoudi, Matthew E. Ritchie, Philip D. Hodgkin, Ashley P. Ng, Stephen L. Nutt, Shalin H. Naik
Summary: The study examines the mechanism of clonal tuning during Flt3L-mediated emergency hematopoiesis, revealing the selective expansion of specific HSPC clones to increase the production of type 1 conventional dendritic cells without affecting other lineages. This is achieved through maintaining proliferative 'early progenitor'-like state in Flt3L-responsive HSPCs, leading to the expansion of transitional cDC1-primed progenitor stages marked by Irf8 expression. The findings define the mechanistic action of Flt3L through clonal tuning, which has important implications for emergency hematopoiesis models.
NATURE CELL BIOLOGY
(2021)
Article
Immunology
Luyi Tian, Sara Tomei, Jaring Schreuder, Tom S. Weber, Daniela Amann-Zalcenstein, Dawn S. Lin, Jessica Tran, Cindy Audiger, Mathew Chu, Andrew Jarratt, Tracy Willson, Adrienne Hilton, Ee Shan Pang, Timothy Patton, Madison Kelly, Shian Su, Quentin Gouil, Peter Diakumis, Melanie Bahlo, Toby Sargeant, Lev M. Kats, Philip D. Hodgkin, Meredith O'Keeffe, Ashley P. Ng, Matthew E. Ritchie, Shalin H. Naik
Summary: This study developed clonal multi-omics to allow multiple independent assays per clone, and identified genes controlling fate bias for different dendritic cell subtypes. Bcor was found to suppress the numbers and development of specific dendritic cell subtypes, offering insights into the molecular and cellular mechanisms governing clonal fate.
Article
Multidisciplinary Sciences
Katie A. Fennell, Dane Vassiliadis, Enid Y. N. Lam, Luciano G. Martelotto, Jesse J. Balic, Sebastian Hollizeck, Tom S. Weber, Timothy Semple, Qing Wang, Denise C. Miles, Laura MacPherson, Yih-Chih Chan, Andrew A. Guirguis, Lev M. Kats, Emily S. Wong, Sarah-Jane Dawson, Shalin H. Naik, Mark A. Dawson
Summary: Studies have shown that malignant clonal dominance is a cell-intrinsic and heritable property facilitated by the repression of antigen presentation and increased expression of the secretory leukocyte peptidase inhibitor gene (Slpi). Increased transcriptional heterogeneity enables clonal fitness in diverse tissues and immune microenvironments, as well as in the context of clonal competition between genetically distinct clones. Leukemia stem cells (LSCs) display heritable clone-intrinsic properties of high and low clonal output, which contribute to the overall tumor mass.
Article
Immunology
Kaspar Bresser, Lianne Kok, Arpit C. Swain, Lisa A. King, Laura Jacobs, Tom S. Weber, Leila Perie, Ken R. Duffy, Rob J. de Boer, Ferenc A. Scheeren, Ton N. Schumacher
Summary: This study investigates the relationship between replicative history and the formation of distinct CD8(+) memory T cell subgroups. The researchers developed a genetic-tracing approach and found that central memory T (T-CM) cell pool has a higher number of prior divisions compared to the effector memory T cell pool. They also discovered that lowly divided T-CM cells display enriched expression of stem-cell-associated genes, exist in a relatively quiescent state, and are superior in eliciting a proliferative recall response upon activation.
Article
Multidisciplinary Sciences
C. Biben, T. S. Weber, K. S. Potts, J. Choi, D. C. Miles, A. Carmagnac, T. Sargeant, C. A. de Graaf, K. A. Fennell, A. Farley, O. J. Stonehouse, M. A. Dawson, D. J. Hilton, S. H. Naik, S. Taoudi
Summary: By using single cell RNA-Sequencing and in vivo cellular barcoding, researchers have unraveled the ancestral relationships that give rise to the haematopoietic lineages of the yolk sac, the endothelium, and the mesenchyme. They found that blood and endothelial cells emerge from three distinct precursors: the haemangioblast, the mesenchymoangioblast, and a previously undescribed cell type called the haematomesoblast. This study is of great significance for a better understanding of embryonic development and the formation of the hematopoietic system.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Antonin Serrano, Tom Weber, Jean Berthelet, Farrah El-Saafin, Sreeja Gadipally, Emmanuelle Charafe-Jauffret, Christophe Ginestier, John M. Mariadason, Samantha R. Oakes, Kara Britt, Shalin H. Naik, Delphine Merino
Summary: Static cell barcoding was used to compare spontaneous and experimental metastasis assays in breast cancer modelling. The results showed that the two assays led to different clonal outputs, highlighting the importance of considering experimental approaches. The study also revealed divergent clonal outputs and biases inherent to each technique.
COMMUNICATIONS BIOLOGY
(2023)