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
Multidisciplinary Sciences
Rinako Nakagawa, Amparo Toboso-Navasa, Marta Schips, George Young, Leena Bhaw-Rosun, Miriam Llorian-Sopena, Probir Chakravarty, Abdul Karim Sesay, George Kassiotis, Michael Meyer-Hermann, Dinis Pedro Calado
Summary: Affinity maturation in germinal centers depends on efficient positive selection of B cells in the light zone. Different subpopulations of cMyc(+) GC B cells are identified and characterized, with higher-affinity cells diverging towards plasmablasts and lower-affinity cells towards memory B cell precursors. This dynamic process of positive selection leads to the generation of three distinct B cell fates, ensuring clonal diversity for broad protection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biotechnology & Applied Microbiology
Brian L. L. Hie, Varun R. R. Shanker, Duo Xu, Theodora U. J. Bruun, Payton A. A. Weidenbacher, Shaogeng Tang, Wesley Wu, John E. E. Pak, Peter S. S. Kim
Summary: Natural evolution explores vast sequence space for rare mutations, and learning from it can guide artificial evolution. A study found that general protein language models can efficiently evolve human antibodies by suggesting evolutionarily plausible mutations, even without target antigen, binding specificity, or protein structure information. Language-model-guided affinity maturation improved the binding affinities of clinically relevant antibodies up to sevenfold and unmatured antibodies up to 160-fold, with favorable thermostability and viral neutralization activity. The models also guided efficient evolution across diverse protein families and selection pressures.
NATURE BIOTECHNOLOGY
(2023)
Article
Oncology
Daniel A. Zlotoff, Malek Z. O. Hassan, Amna Zafar, Raza M. Alvi, Magid Awadalla, Syed S. Mahmood, Lili Zhang, Carol L. Chen, Stephane Ederhy, Ana Barac, Dahlia Banerji, Maeve Jones-O'Connor, Sean P. Murphy, Merna Armanious, Brian J. Forrestal, Michael C. Kirchberger, Otavio R. Coelho-Filho, Muhammad A. Rizvi, Gagan Sahni, Anant Mandawat, Carlo G. Tocchetti, Sarah Hartmann, Hannah K. Gilman, Eduardo Zatarain-Nicolas, Michael Mahmoudi, Dipti Gupta, Ryan Sullivan, Sarju Ganatra, Eric H. Yang, Lucie M. Heinzerling, Franck Thuny, Leyre Zubiri, Kerry L. Reynolds, Justine Cohen, Alexander R. Lyon, John Groarke, Paaladinesh Thavendiranathan, Anju Nohria, Michael G. Fradley, Tomas G. Neilan
Summary: In ICI myocarditis, the QRS duration is prolonged and associated with increased MACE risk, while there is no association between the QTc interval and MACE.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Immunology
Rinako Nakagawa, Dinis Pedro Calado
Summary: Germinal centers play a crucial role in the production of high-affinity antibody secreting plasma cells and memory-B cells for vaccination. The positive selection process in GCs guides B cell fates towards becoming either PCs, MBCs or persistent GC-B cells, with each cell type playing a specific role in the immune response.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Qi Ke, Ashley Nicole Greenawalt, Veera Manukonda, Xingqi Ji, Roland Michael Tisch
Summary: Inflammasome molecules are receptors that trigger proinflammatory responses against microbial infections. Dysregulation of inflammasome activity has been associated with chronic inflammation and autoimmune diseases. Inflammasome activation affects both innate and adaptive immune effectors as well as resident cells in target tissues, contributing to autoimmune responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Deniz Cizmeci, Giuseppe Lofano, Evan Rossignol, Anne-Sophie Dugast, Dongkyoon Kim, Guy Cavet, Ngan Nguyen, Yann Chong Tan, Michael S. Seaman, Galit Alter, Boris Julg
Summary: A subset of individuals infected with HIV-1 develop antibody neutralization breadth during the natural course of infection, often linked to chronic high viremia. Despite efforts, vaccination strategies have not been able to induce similar breadth, with broadly neutralizing antibody responses also found in individuals controlling HIV infection without antiretroviral therapy.
Article
Biochemical Research Methods
Gustavo Hernandez-Mejia, Esteban A. Hernandez-Vargas
Summary: The research team developed a stochastic model that successfully represents antibody cross-reactive data and validated it with cross-reaction data of different influenza strains. They found that changes in time of infection and the B-cells population are important for successful antibody cross-reaction, while the affinity threshold of B-cells between consecutive infections is a necessary condition.
Article
Immunology
Raud Razzaghi, Shreya Agarwal, Nikita Kotlov, Olga Plotnikova, Krystle Nomie, Da Wei Huang, George W. Wright, Grace A. Smith, Moyi Li, Katsuyoshi Takata, Maryam Yamadi, Chen Yao, John J. O'Shea, James D. Phelan, Stefania Pittaluga, David W. Scott, Jagan R. Muppidi
Summary: The study indicates that Fas serves as an intrinsic regulator in GC B cells and plays a crucial role in maintaining GC homeostasis. Mutations in FAS are associated with poor prognosis, enrichment of Tfh cells, and deficiencies in HVEM and PD-L1 in GC-derived DLBCL.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Renan V. H. de Carvalho, Jonatan Ersching, Alexandru Barbulescu, Alvaro Hobbs, Tiago B. R. Castro, Luka Mesin, Johanne T. Jacobsen, Brooke K. Phillips, Hans -Heinrich Hoffmann, Roham Parsa, Maria Cecilia C. Canesso, Carla R. Nowosad, Allan Feng, Sarah R. Leist, Ralph S. Baric, Emily Yang, P. J. Utz, Gabriel D. Victora
Summary: Long-lasting germinal centers (LLGCs) generated by respiratory virus infection are sustained by continuous replacement of B cell clones, and highly mutated antibodies are enriched in rare founder clones that resist replacement. These LLGCs are maintained by invader B cells that don't bind viral antigens and can produce highly mutated immunoglobulins. This study reveals previously unappreciated aspects of LLGC biology and identifies clonal replacement as a potential constraint on the development of highly mutated antibodies.
Article
Immunology
Elise R. Breed, Matous Voboril, Katherine M. Ashby, Ryan J. Martinez, Lily Qian, Haiguang Wang, Oscar C. Salgado, Christine H. O'Connor, Kristin A. Hogquist
Summary: Researchers have identified a subset of thymic dendritic cells that express CD301b and contribute to thymic tolerance. These cells have enhanced antigen processing and presentation, and their activation is induced by type II cytokines. Selective deletion of these cells impairs conventional T cell deletion in the thymus without affecting regulatory T cell selection. These findings highlight the importance of cytokine-induced activation of dendritic cells in central tolerance.
Article
Multidisciplinary Sciences
Nathan T. Mortimer, Mary L. Fischer, Ashley L. Waring, K. R. Pooja, Balint Z. Kacsoh, Susanna E. Brantley, Erin S. Keebaugh, Joshua Hill, Chris Lark, Julia Martin, Pravleen Bains, Jonathan Lee, Alysia D. Vrailas-Mortimer, Todd A. Schlenke
Summary: In order to combat infections, hosts must differentiate pathogens from their own tissues and maintain the stability of their immune system. Research has found that aberrant autoimmunity in Drosophila is caused by two gene mutations, providing insights into the understanding of self-recognition systems in animals.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Shuai Liu, Yu-mei Li, Jin-zhi Li, Shu-jun Wang, Ping Ji, Mei-yu Zhang, Ying Wang
Summary: This study investigates the role of CD4(+) T cells in antibody production in a lupus-like mouse model and reveals their importance in promoting IgG production.
MEDIATORS OF INFLAMMATION
(2022)
Article
Immunology
Timm Amendt, Omar El Ayoubi, Alexandra T. Linder, Gabriele Allies, Marc Young, Corinna S. Setz, Hassan Jumaa
Summary: IgD-deficient mice have an accelerated rate of B cell responsiveness and can activate antibody production within 24 hours after immunization, while wildtype mice require 3 days to activate antibody responses. IgD-deficient mice are unable to modulate antibody production, suggesting that IgD controls the activation rate of B cells and subsequent antibody production by sensing and distinguishing antigen valences.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Nora Langreder, Dorina Schaeckermann, Doris Meier, Marlies Becker, Maren Schubert, Stefan Duebel, Thomas Reinard, Stefanie Figge-Wegener, Kristine Rossbach, Wolfgang Baeumer, Simone Ladel, Michael Hust
Summary: Insect bite hypersensitivity (IBH), the most common allergic skin disease in horses, is caused by bites from Culicoides spp. insects, resulting in a type I/IVb allergy involving eosinophil cells. A potential treatment option is the use of a therapeutic antibody targeting equine interleukin 5, the main activator and regulator of eosinophils. Through phage display and in vitro affinity maturation, an antibody named NOL226-2-D10 was developed, showing strong inhibition of interleukin 5 binding and satisfactory producibility. This antibody is a promising candidate for in vivo studies to treat equine IBH.
SCIENTIFIC REPORTS
(2023)
Article
Psychology, Clinical
Arthur Montalto, Haeme R. P. Park, Leanne M. Williams, Mayuresh S. Korgaonkar, Miranda R. Chilver, Javad Jamshidi, Peter R. Schofield, Justine M. Gatt
Summary: The study found that greater resilience to trauma is associated with less activation of the anterior insula during a condition requiring sustained attention. This possibly suggests a pattern of 'neural efficiency' in people who may be more resilient to trauma.
PSYCHOLOGICAL MEDICINE
(2023)
Editorial Material
Immunology
Veerle Somers, Deborah K. Dunn-Walters, Mirjam van der Burg, Judith Fraussen
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Sebastian R. Schulz, Markus Hoffmann, Edith Roth, Katharina Pracht, Deborah L. Burnett, Ohan Mazigi, Wolfgang Schuh, Bernhard Manger, Dirk Mielenz, Christopher C. Goodnow, Daniel Christ, Stefan Poehlmann, Hans-Martin Jaeck
Summary: In this study, the efficacy of boost immunization with BNT162b2 and therapeutic antibodies in neutralizing the Omicron variant was determined using flow cytometry-based assays. The results showed that a third vaccination with BNT162b2 increased the amount of neutralizing antibodies against the Omicron variant, although to a lesser degree compared to the parental strain. Additionally, most clinically approved therapeutic antibodies failed to recognize and neutralize the Omicron variant, while some antibodies under preclinical development showed potential in neutralizing it.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
David B. Langley, Peter Schofield, Jenny Jackson, Herbert Herzog, Daniel Christ
Summary: Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) are evolutionarily conserved pancreatic polypeptides. Using a crystallization chaperone, the structures of human NPY and human PYY were successfully determined. The structure of human PYY closely resembles that of avian PP, while the structure of human NPY is different.
Article
Cardiac & Cardiovascular Systems
Julien Solinc, Jessica Raimbault-Machado, France Dierick, Lamiaa El Bernoussi, Ly Tu, Raphael Thuillet, Nathalie Mougenot, Benedicte Hoareau-Coudert, Virginie Monceau, Catherine Pavoine, Fabrice Atassi, David Sassoon, Giovanna Marazzi, Richard P. Harvey, Peter Schofield, Daniel Christ, Marc Humbert, Christophe Guignabert, Florent Soubrier, Sophie Nadaud
Summary: This study demonstrates the significant role of the platelet-derived growth factor receptor alpha (PDGFR alpha) pathway in progenitor cell-dependent vascular remodeling and neomuscularization associated with pulmonary arterial hypertension (PAH). Inhibition of PDGFR alpha activity reduces pulmonary vessel neomuscularization, while constitutive activation of PDGFR alpha leads to neomuscularization and PH development. These findings suggest that PDGFR alpha blockers may be a promising therapeutic strategy for reducing vascular remodeling in PAH patients.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Multidisciplinary Sciences
Cecile F. Frampas, Katie Longman, Matt Spick, Holly-May Lewis, Catia D. S. Costa, Alex Stewart, Deborah Dunn-Walters, Danni Greener, George Evetts, Debra J. Skene, Drupad Trivedi, Andy Pitt, Katherine Hollywood, Perdita Barran, Melanie J. Bailey
Summary: Saliva metabolomics, particularly amino acids, can differentiate between high severity and low severity COVID-19 patients, expanding the understanding of COVID-19 metabolic dysregulation and potentially providing a non-invasive means of sampling patients for timely treatment.
Article
Immunology
Weng Hua Khoo, Katherine Jackson, Chansavath Phetsouphanh, John J. Zaunders, Jose Alquicira-Hernandez, Seyhan Yazar, Stephanie Ruiz-Diaz, Mandeep Singh, Rama Dhenni, Wunna Kyaw, Fiona Tea, Vera Merheb, Fiona X. Z. Lee, Rebecca Burrell, Annaleise Howard-Jones, Archana Koirala, Li Zhou, Aysen Yuksel, Daniel R. Catchpoole, Catherine L. Lai, Tennille L. Vitagliano, Romain Rouet, Daniel Christ, Benjamin Tang, Nicholas P. West, Shane George, John Gerrard, Peter Croucher, Anthony D. Kelleher, Christopher G. Goodnow, Jonathan D. Sprent, Joseph E. Powell, Fabienne Brilot, Ralph Nanan, Peter S. Hsu, Elissa K. Deenick, Philip N. Britton, Tri Giang Phan
Summary: Children infected with SARS-CoV-2 develop milder COVID-19 compared to adults. Analysis of T cells shows that children have a smaller immune response, with diverse naive T cells, while adults have memory T cells. This suggests that rapid clearance of the virus in children may compromise their ability to develop long-term immunity.
CLINICAL IMMUNOLOGY
(2023)
Article
Cell Biology
Money Gupta, Harikrishnan Balachandran, Raymond H. Y. Louie, Hui Li, David Agapiou, Elizabeth Keoshkerian, Daniel Christ, William Rawlinson, Michael M. Mina, Jeffrey J. Post, Bernard Hudson, Nicky Gilroy, Pamela Konecny, Adam W. Bartlett, Sarah C. Sasson, Golo Ahlenstiel, Dominic Dwyer, Andrew R. Lloyd, Marianne Martinello, Fabio Luciani, Rowena A. Bull
Summary: This study analyzed the molecular and phenotypic properties of SARS-CoV-2 receptor-binding domain (RBD)-specific memory B cells (MBCs) in COVID-19 patients. The results showed differences between severe and mild/moderate groups, with the severe group exhibiting a higher level of tumor necrosis factor-alpha (TNF-alpha) signaling, indicating persistent dysfunctional features in convalescence.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Immunology
Simona Ceglia, Alyssa Berthelette, Kelsey Howley, Yun Li, Benedikt Mortzfeld, Shakti K. Bhattarai, Nicole K. H. Yiew, Ying Xu, Robert Brink, Jason G. Cyster, Lora V. Hooper, Gwendalyn J. Randolph, Vanni Bucci, Andrea Reboldi
Summary: Research shows that high-cholesterol diets can influence IgA secretion. Cholesterol-derived metabolites affect the positioning of IgA(+) plasma cells and suppress antibody responses to intestinal pathogens by acting on GPR183 receptors.
Article
Biochemistry & Molecular Biology
Abigail K. Grootveld, Wunna Kyaw, Veera Panova, Angelica W. Y. Lau, Emily Ashwin, Guillaume Seuzaret, Rama Dhenni, Nayan Deger Bhattacharyya, Weng Hua Khoo, Mate Biro, Tanmay Mitra, Michael Meyer-Hermann, Patrick Bertolino, Masato Tanaka, David A. Hume, Peter I. Croucher, Robert Brink, Akira Nguyen, Oliver Bannard, Tri Giang Phan
Summary: Germinal centers (GCs) in lymphoid follicles during antibody responses are areas of extensive cell death. Tingible body macrophages (TBMs) derived from lymph node-resident, CD169-lineage, CSF1R-blockade-resistant precursor. Non-migratory TBMs use cytoplasmic processes to capture migrating dead cell fragments using a lazysearch strategy. Follicular macrophages can mature into TBMs in the absence of GCs and activated by the nearby apoptotic cells. Single-cell transcriptomics analysis identified upregulated genes related to apoptotic cell clearance in TBMs, which prevent autoimmune diseases.
Article
Immunology
Michela Frascoli, Enxhi Ferraj, Bing Miu, Justin Malin, Nicholas A. Spidale, Jennifer Cowan, Susannah C. Shissler, Robert Brink, Ying Xu, Jason G. Cyster, Avinash Bhandoola, Joonsoo Kang, Andrea Reboldi
Summary: Dietary components and metabolites greatly influence immunity and inflammation. This study focuses on how cholesterol metabolite oxysterols sensed by y8 T cells impact their tissue residency and function. The findings suggest that oxysterols sensing through G protein receptor 183 (GPR183) is essential for the development and inflammatory responses of dermal IL-17-producing y8 T (Ty817) cells, which are crucial for skin-barrier homeostasis.
Article
Multidisciplinary Sciences
Romain Rouet, Jake Y. Henry, Matt D. Johansen, Meghna Sobti, Harikrishnan Balachandran, David B. Langley, Gregory J. Walker, Helen Lenthall, Jennifer Jackson, Stephanie Ubiparipovic, Ohan Mazigi, Peter Schofield, Deborah L. Burnett, Simon H. J. Brown, Marianne Martinello, Bernard Hudson, Nicole Gilroy, Jeffrey J. Post, Anthony Kelleher, Hans-Martin Jaeck, Christopher C. Goodnow, Stuart G. Turville, William D. Rawlinson, Rowena A. Bull, Alastair G. Stewart, Philip M. Hansbro, Daniel Christ
Summary: Rouet et al. developed a strategy to identify broadly neutralising antibodies against the SARS-CoV-2 receptor binding domain from convalescent patients. They discovered a new class 6 epitope and demonstrated that these antibodies can be isolated from the patients' peripheral blood. The identified antibodies effectively neutralise emerging variants of concern and outperform the clinical monoclonal antibody sotrovimab in potency. This research provides insights for the development of next generation monoclonal antibodies and vaccines.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Etienne Masle-Farquhar, Yogesh Jeelall, Jacqueline White, Julia Bier, Elissa K. Deenick, Robert Brink, Keisuke Horikawa, Christopher Carl Goodnow
Summary: This study investigated the effects of CARD11 gene mutations on B and T lymphocytes in a disease associated with B cell expansion and T cell anergy, as well as in certain lymphomas. The results showed that the mutations increased the activation and proliferation of B and T lymphocytes following antigen receptor stimulation, and led to increased expression of checkpoint molecules on T cells. This study reveals CARD11 as an important positive regulator of T cells and highlights the cell-intrinsic effects of CARD11 mutations on T cell malignancies.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Sacha Zinn, Rodrigo Vazquez-Lombardi, Carsten Zimmermann, Puja Sapra, Lutz Jermutus, Daniel Christ
Summary: In this review article, Christ and colleagues discuss recent developments in antibody-based cancer therapies. Monoclonal antibodies, characterized by their specificity, long serum half-life, high affinity, and immune effector functions, are an ever-growing class of targeted cancer therapeutics. The authors outline key advances in the field, focusing on engineered antibody therapeutic candidates, and provide updates on their molecular structure, mechanisms of action, clinical development, and practice.
Article
Biochemistry & Molecular Biology
Peter Schofield, Alexander Taylor, Jerome Rihon, Cristian D. Pena Martinez, Sacha Zinn, Charles-Alexandre Mattelaer, Jennifer Jackson, Gurpreet Dhaliwal, Guy Schepers, Piet Herdewijn, Eveline Lescrinier, Daniel Christ, Philipp Holliger
Summary: Nucleic acids serve as the basis of heredity and are increasingly utilized to create novel nanostructures, devices, and drugs. Chemically modified alternatives, known as xeno nucleic acids (XNAs), have been developed to expand their chemical and functional capabilities. XNA aptamers, which can bind targets with high affinity and specificity, have not been thoroughly investigated in terms of their structure and function.
NUCLEIC ACIDS RESEARCH
(2023)