Article
Immunology
Kenneth Green, Thomas R. Wittenborn, Cecilia Fahlquist-Hagert, Ewa Terczynska-Dyla, Nina van Campen, Lisbeth Jensen, Line Reinert, Rune Hartmann, Soren R. Paludan, Soren E. Degn
Summary: Germinal centers (GCs) are essential for the quality of the antibody response to infections and vaccines. The cGAS-STING pathway plays a crucial role in B cell responses, impacting GC B cells and antibody production. Understanding the role of this pathway may have implications for vaccine design and autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Teresa Fuertes, Irene Salgado, Virginia G. de Yebenes
Summary: miRNAs play crucial roles in regulating GC responses, influencing the physiological processes of B cells and T follicular helper cells, as well as diseases associated with dysregulation of GC responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Allergy
Pengpeng Cao, Ming Yang, Christopher Chang, Haijing Wu, Qianjin Lu
Summary: This review provides an overview of the role of GPCRs in GC reactions and their ligands, as well as their impact on antibody-mediated autoimmune skin diseases. Furthermore, the importance of GPCRs as drug targets is discussed.
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
(2022)
Editorial Material
Immunology
Cecilia Fahlquist-Hagert, Thomas R. Wittenborn, Alexey Ferapontov, Lisbeth Jensen, Ewa Terczynska-Dyla, Soren E. Degn
Summary: Using an autoimmune bone marrow chimera model, this study found that B cells heavily rely on MHCII expression for their participation in the germinal center. However, cells with a 50% reduction in surface MHCII can still compete efficiently with wild-type cells.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
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.
Article
Immunology
Wen-Wu Li, Yang Yang, Tian-Zhi Guo, Peyman Sahbaie, Xiao-you Shi, Qin Guang, Wade S. Kingery, Leonore A. Herzenberg, J. David Clark
Summary: In a murine tibia fracture model of complex regional pain syndrome (CRPS), up-regulated IL-6 signaling was found to be crucial for the development of nociceptive sensitization, vascular changes, and IgM immune complex deposition in the injured limbs. These findings suggest that anti-IL-6 therapies may be effective in reducing pain in the context of limb fracture or CRPS.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Immunology
Prachi Bagadia, Kevin W. O'Connor, Renee Wu, Stephen T. Ferris, Jeffrey P. Ward, Robert D. Schreiber, Theresa L. Murphy, Kenneth M. Murphy
Summary: Bcl6 is required for the development of a subset of cDC1-specific markers in vitro but not in vivo. Its deficiency selectively reduces CD8 alpha expression in cDC1 without affecting XCR1 or CD24 expression.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Camilla Wibrand, Thomas R. Wittenborn, Lasse Frank Voss, Gudrun Winther, Lisbeth Jensen, Alexey Ferapontov, Sofie V. Fonager, Cecilia Fahlquist-Hagert, Soren E. Degn
Summary: This study demonstrates that B cell intrinsic MHC haplotype governs their capacity for participation in the autoimmune response at multiple levels: follicular inclusion, GC participation, and PC output. These findings pinpoint B cells as central contributors to the precipitation of autoimmunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Yisi Lu, Joe Craft
Summary: T follicular regulatory cells are a unique subset of regulatory T cells that migrate to B cell follicles and germinal centers to maintain immune homeostasis. They use specific transcription factors to regulate immune responses, promoting humoral immunity and memory following viral infections.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Patrick Daum, Shannon R. Ottmann, Julia Meinzinger, Sebastian R. Schulz, Joana Corte-Real, Manuela Hauke, Edith Roth, Wolfgang Schuh, Dirk Mielenz, Hans-Martin Jaeck, Katharina Pracht
Summary: It has been demonstrated through experiments that DGCR8 is crucial for T cell-mediated antibody responses, with a greater impact on B2 cells. However, the deletion of DGCR8 in B1 cells is incomplete, providing a model for studying B1 cell responses in the absence of functional B2 cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Kristen M. Valentine, Genevieve N. Mullins, Oscar A. Davalos, Lek Wei Seow, Katrina K. Hoyer
Summary: CD8 Tfc, a unique subset of CD8 T cells, are polyfunctional during autoimmune disease, producing helper cytokines and maintaining cytolytic proteins, contributing to pathogenic autoimmune B cell response.
JOURNAL OF AUTOIMMUNITY
(2021)
Article
Immunology
Angelica W. Y. Lau, Vivian M. Turner, Katherine Bourne, Jana R. Hermes, Tyani D. Chan, Robert Brink
Summary: The BAFF/BAFFR signaling pathway is necessary for the generation of unmutated, GC-independent MBCs derived directly from activated B cells, while not affecting GC B cells or GC-derived MBCs. Both types of MBCs require input from this pathway for optimal long-term survival.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Marianne Dolz, Marko Hasiuk, John D. Gagnon, Mara Kornete, Romina Marone, Glenn Bantug, Robin Kageyama, Christoph Hess, K. Mark Ansel, Denis Seyres, Julien Roux, Lukas T. Jeker
Summary: CD28 provides the prototypical costimulatory signal for T cell activation. miR-17 similar to 92, induced by T cell receptor stimulation and enhanced by CD28 costimulation, acts as a central mediator for T cell activation by dampening negative regulators.
Article
Immunology
Elliott D. SoRelle, Nicolas M. Reinoso-Vizcaino, Gillian Q. Horn, Micah A. Luftig
Summary: This study investigated the impact of Epstein-Barr virus (EBV) on B cell heterogeneity, emphasizing the dynamic and complexity of the infection. The research found that EBV continuously drives B cell entry, progression through, and egress from the Germinal Center reaction, potentially leading to autoimmune disorders.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Seung-Chul Choi, Wei Li, Xiaojuan Zhang, Nathalie Kanda, Leilani Zeumer-Spataro, Xiangyu Teng, Laurence Morel
Summary: This study found that B cells in lupus-prone mice have enhanced glycolysis and mitochondrial respiration before the onset of autoimmunity, which can be normalized by inhibiting glycolysis with 2DG treatment. B cells have a greater requirement for glycolysis in T cell-independent immune responses, but not in T cell-dependent immune responses. Targeting glucose metabolism may provide an effective therapeutic approach for lupus by eliminating autoreactive B cells and follicular Th cells.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Samuel W. Du, Tanvi Arkatkar, Fahd Al Qureshah, Holly M. Jacobs, Christopher D. Thouvenel, Kristy Chiang, Andrea D. Largent, Quan-Zhen Li, Baidong Hou, David J. Rawlings, Shaun W. Jackson
JOURNAL OF IMMUNOLOGY
(2019)
Article
Immunology
Patricia M. Santos, Juraj Adamik, Timothy R. Howes, Samuel Du, Lazar Vujanovic, Sarah Warren, Andrea Gambotto, John M. Kirkwood, Lisa H. Butterfield
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Article
Immunology
Christopher D. Thouvenel, Mary F. Fontana, Jason Netland, Akshay T. Krishnamurty, Kennidy K. Takehara, Yu Chen, Suruchi Singh, Kazutoyo Miura, Gladys J. Keitany, Eric M. Lynch, Silvia Portugal, Marcos C. Miranda, Neil P. King, Justin M. Kollman, Peter D. Crompton, Carole A. Long, Marie Pancera, David J. Rawlings, Marion Pepper
Summary: This study demonstrates the potential of high-avidity IgM antibodies in both therapeutics and vaccines. Forced multimerization of IgG antibodies significantly improved antigen binding and parasite restriction, highlighting how avidity can alter antibody function.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Immunology
Holly M. Jacobs, Tanvi Arkatkar, Samuel W. Du, Nicole E. Scharping, Jonathan Woods, Quan-Zhen Li, Kelly L. Hudkins, Charles E. Alpers, David J. Rawlings, Shaun W. Jackson
Summary: Polymorphisms in TACI are associated with various human immune disorders, with subtle variations impacting B-cell biology. The complexity of TACI biology involves both positive and negative regulation of physiological and pathogenic B-cell responses.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Samagya Banskota, Aditya Raguram, Susie Suh, Samuel W. Du, Jessie R. Davis, Elliot H. Choi, Xiao Wang, Sarah C. Nielsen, Gregory A. Newby, Peyton B. Randolph, Mark J. Osborn, Kiran Musunuru, Krzysztof Palczewski, David R. Liu
Summary: We have developed and applied engineered DNA-free virus-like particles (eVLPs) for efficient delivery of gene editing tools, achieving high levels of base editing. By overcoming the limitations of cargo packaging, release, and localization, the fourth-generation eVLPs demonstrated efficient base editing in mouse and human cells. In addition, the off-target effects of eVLPs were significantly reduced compared to other delivery methods such as AAV or plasmid.
Review
Neurosciences
Samuel W. Du, Krzysztof Palczewski
Summary: MicroRNAs are short, evolutionarily conserved noncoding RNAs that are critical for controlling normal cellular physiology. Recent research has highlighted their role in supporting retina function through regulating RPE activities. They have potential applications as therapeutics and biomarkers for visual diseases.
TRENDS IN NEUROSCIENCES
(2022)
Article
Multidisciplinary Sciences
Elliot H. Choi, Susie Suh, Andrzej T. Foik, Henri Leinonen, Gregory A. Newby, Xin D. Gao, Samagya Banskota, Thanh Hoang, Samuel W. Du, Zhiqian Dong, Aditya Raguram, Sajeev Kohli, Seth Blackshaw, David C. Lyon, David R. Liu, Krzysztof Palczewski
Summary: The study demonstrates that in vivo base editing can prolong the survival of cone photoreceptors and restore their function in a mouse model of Leber congenital amaurosis.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Malika Hale, Jason Netland, Yu Chen, Christopher D. Thouvenel, Katherine Nabel Smith, Lucille M. Rich, Elizabeth R. Vanderwall, Marcos C. Miranda, Julie Eggenberger, Linhui Hao, Michael J. Watson, Charles C. Mundorff, Lauren B. Rodda, Neil P. King, Miklos Guttman, Michael Gale, Jonathan Abraham, Jason S. Debley, Marion Pepper, David J. Rawlings
Summary: Using monoclonal antibodies built from SARS-CoV-2-specific memory B cells, Hale et al. demonstrate that IgM antibodies outperform IgG in neutralization assays against mutated variants. The authors suggest that IgM antibodies may be useful therapeutically, and that IgM memory B cells may be underappreciated protectors against rapidly evolving pathogens.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Editorial Material
Immunology
Samuel W. W. Du, Krzysztof Palczewski
Summary: CRISPR/Cas9 genome editing techniques have the potential to treat previously untreatable inherited genetic disorders of vision by correcting mutations that cause these afflictions. Using a prime editor, Qin et al. (2023. J. Exp. Med. https://doi.org/10.1084/jem.20220776) restored visual functions in a mouse model (rd10) of retinitis pigmentosa.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Cell Biology
Andrea D. Largent, Katharina Lambert, Kristy Chiang, Natali Shumlak, Denny Liggitt, Mohammed Oukka, Troy R. Torgerson, Jane H. Buckner, Eric J. Allenspach, David J. Rawlings, Shaun W. Jackson
Summary: Heterozygous gain-of-function mutations in STAT1 promote immune dysregulation with recurrent infections and humoral autoimmunity. Deep immunophenotyping in pediatric patients and transgenic mice revealed dysregulated CD4(+) T cell and B cell activation, with expansion of T(H)1-skewed CXCR3(+) populations. Autoimmunity in STAT1 GOF syndrome is driven by dysregulated STAT1-dependent signals downstream of type 1 and type 2 interferon receptors, with IFN-? as the critical driver of feedforward STAT1 elevation.
SCIENCE TRANSLATIONAL MEDICINE
(2023)