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
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
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
Julia Merkenschlager, Riza-Maria Berz, Victor Ramos, Maximilian Uhlig, Andrew J. Maclean, Carla R. Nowosad, Thiago Y. Oliveira, Michel C. Nussenzweig
Summary: This study found that follicular helper and regulatory T cells are continuously recruited into germinal centers during the germinal center reaction, and they quantitatively contribute to the remodeling of germinal centers.
NATURE COMMUNICATIONS
(2023)
Article
Physics, Multidisciplinary
Hongda Jiang, Shenshen Wang
Summary: The adaptive immune system improves its protection against future pathogens by constantly modifying its lymphocyte repertoire. Recent experiments have shown that B cells physically extract antigens using active forces, and this extraction level determines clonal fitness. These observations challenge the prevailing view that the equilibrium constant of receptor-antigen binding determines selective advantage. A theoretical framework was proposed to explore the impact of tug-of-war antigen extraction on the quality and diversity of an evolved B cell repertoire. The results suggest that active forces play a multifaceted role in immune adaptation, rationalizing key observations on repertoire dynamics.
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
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
Chemistry, Multidisciplinary
Hongyu Liu, Huixin Luo, Qi Xue, Shan Qin, Shuang Qiu, Shibo Liu, Jian Lin, Jie P. Li, Peng R. Chen
Summary: This study presents a method for the detection and quantification of cell-cell interactions using photocatalytic labeling, which allows the labeling of interacting cells and provides insights into immune responses and immunotherapy development.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
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)
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
Zoe Steier, Dominik A. Aylard, Laura L. McIntyre, Isabel Baldwin, Esther Jeong Yoon Kim, Lydia K. Lutes, Can Ergen, Tse-Shun Huang, Ellen A. Robey, Nir Yosef, Aaron Streets
Summary: Streets, Yosef, Robey and colleagues used multiomics analysis to establish a comprehensive timeline of the development of CD4(+) and CD8(+) T cells lineage commitment. They identified sequential waves of TCR signaling that initiate CD4(+) T cell lineage differentiation followed by CD8(+) T cell lineage specification. Their findings provide valuable insights into cell fate decisions and suggest a sequential selection process in guiding lineage choice.
Review
Immunology
Brittany Henry, Brian J. Laidlaw
Summary: Vaccines can generate antibody and memory B-cell responses for protective immunity. However, antibody levels decrease over time, leading to the need for booster vaccines. Memory B-cells can persist after vaccination and quickly produce antibody-secreting cells or undergo maturation upon antigen re-encounter. Repeated antigen exposure results in memory B-cells encoding antibodies capable of broadly protective immunity against viruses like SARS-CoV-2 and influenza. In this review, we highlight emerging evidence showing the heterogeneity of memory B-cells and their distinct roles in mediating protective immunity upon antigen re-encounter, and discuss the implications for developing vaccines that elicit broadly protective immunity.
CURRENT OPINION IN IMMUNOLOGY
(2023)
Article
Cell Biology
Yupeng Feng, Meng Yuan, John M. Powers, Mengyun Hu, Jennifer E. Munt, Prabhu S. Arunachalam, Sarah R. Leist, Lorenza Bellusci, JungHyun Kim, Kaitlin R. Sprouse, Lily E. Adams, Sumana Sundaramurthy, Xueyong Zhu, Lisa M. Shirreff, Michael L. Mallory, Trevor D. Scobey, Alberto Moreno, Derek T. O'Hagan, Harry Kleanthous, Francois J. Villinger, David Veesler, Neil P. King, Mehul S. Suthar, Surender Khurana, Ralph S. Baric, Ian A. Wilson, Bali Pulendran
Summary: This study identified highly potent monoclonal antibodies (mAbs) from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines that neutralized multiple sarbecoviruses. The antibodies generated from antigen-specific memory B cells (MBCs) exhibited increasing potency and breadth over a period of 8-15 months after vaccination. Some of the antibodies also showed neutralizing activity against the SARS-CoV-2 BA.1 variant. Crystallography studies revealed the molecular basis of the broad and potent neutralization.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Kaho Kajiwara, Wataru Aoki, Naoki Koike, Mitsuyoshi Ueda
Summary: This study developed a modified YSD method utilizing SpyTag/SpyCatcher-based in vivo protein ligation, achieving a high display efficiency of more than 90%, no intercellular protein ligation events, and enrichment of target cells by cell sorting. These results suggest that this system performs comparably with conventional YSD methods and can be integrated with in vivo continuous evolution.
SCIENTIFIC REPORTS
(2021)
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)