Article
Immunology
Jana Koers, Casper Marsman, Juulke Steuten, Simon Tol, Ninotska I. L. Derksen, Anja ten Brinke, S. Marieke van Ham, Theo Rispens
Summary: In this study, the researchers used optimized in vitro culture conditions and in-depth assessment of B cell characteristics and signaling pathways to investigate the role of oxygen in regulating human naive B cell differentiation and class switch recombination. They found that normoxia promotes differentiation into functional antibody secreting cells, while a unique population of CD27(++) B cells is generated under hypoxia. Additionally, time-dependent transitions between hypoxic and normoxic oxygen levels during culture can direct different trajectories of human B cell differentiation and IgG class switch recombination.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Chloe Oudinet, Xuefei Zhang, Nadine Puget, Nia Kyritsis, Claire Leduc, Fatima-Zohra Braikia, Audrey Dauba, Frederick W. Alt, Ahmed Amine Khamlichi
Summary: Immunoglobulin class switch recombination plays a crucial role in humoral immune responses by altering the effector functions of antibodies. The A-NHEJ pathway in CSR shows a preference for longer junctional micro-homologies, and the molecular basis of S mu specificity remains unclear. Introducing the E mu enhancer into the S gamma 3 region confers the recombinational features of S mu to S gamma 3, indicating a bias for longer MH.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Yuexia Liao, Lijuan Fan, Peng Bin, Congrui Zhu, Qingyi Chen, Yepeng Cai, Jielin Duan, Qian Cai, Wei Han, Shizhen Ding, Xiangyu Hu, Yiran Zhang, Yulong Yin, Wenkai Ren
Summary: Recent findings suggest potential connections between neurotransmitters, intestinal mucosal immune responses, and the development of IgA nephropathy (IgAN). This study demonstrates that deficiency of the gamma-amino butyric acid transporter-2 (GAT-2) enhances the differentiation of germinal center (GC) B cells in the intestines and worsens the symptoms of IgAN in a mouse model. Additionally, IgAN patients have lower GAT-2 expression and higher activation of the mammalian target of rapamycin complex 1 (mTORC1) in blood B cells, both of which are correlated with kidney function in IgAN patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Ellen D. Renner, Carolin E. Kraetz, Jordan S. Orange, Beate Hagl, Stacey Rylaarsdam, Gundula Notheis, Anne Durandy, Troy R. Torgerson, Hans D. Ochs
Summary: This study evaluated the correlation between B cell phenotype analysis and antigen responses in patients with CSRD, finding distinct patterns of antibody responses to a new antigen among different types of CSRD patients.
CLINICAL IMMUNOLOGY
(2021)
Article
Immunology
Pascal Irrgang, Juliane Gerling, Katharina Kocher, Dennis Lapuente, Philipp Steininger, Katharina Habenicht, Monika Wytopil, Stephanie Beileke, Simon Schaefer, Jahn Zhong, George Ssebyatika, Thomas Krey, Valeria Falcone, Christine Schuelein, Antonia Sophia Peter, Krystelle Nganou-Makamdop, Hartmut Hengel, Juergen Held, Christian Bogdan, Klaus Ueberla, Kilian Schober, Thomas H. Winkler, Matthias Tenbusch
Summary: RNA vaccines are effective in preventing SARS-CoV-2 infection, and high levels of neutralizing antibodies are crucial for vaccine-induced immunity. After the second mRNA vaccination, SARS-CoV-2-specific antibodies were increasingly composed of noninflammatory IgG4, which was further boosted by a third vaccination or breakthrough infections. This induction of IgG4 antibodies was not observed with adenoviral vectors. These findings have implications for the choice and timing of mRNA vaccine regimens, including booster shots.
SCIENCE IMMUNOLOGY
(2023)
Article
Biology
Michael Jonathan Lehrke, Michael Jeremy Shapiro, Matthew J. Rajcula, Madeleine M. Kennedy, Shaylene A. McCue, Kay L. Medina, Virginia Smith Shapiro
Summary: ABCB7 is essential for early B cell development, proliferation, and class switch recombination. Loss of ABCB7 results in replication-induced DNA damage and slowed DNA replication in pro-B cells.
Article
Immunology
Christopher C. Udoye, Christina N. Rau, Sarah M. Freye, Larissa N. Almeida, Sarah Vera-Cruz, Kai Othmer, Rabia Ue Korkmaz, Ann-Katrin Clauder, Timo Lindemann, Markus Niebuhr, Fabian Ott, Kathrin Kalies, Andreas Recke, Hauke Busch, Anke Faehnrich, Fred D. Finkelman, Rudolf A. Manz
Summary: The study analyzed the IgE response in murine food allergy and found that an ongoing unmutated extrafollicular IgE response coexists with a germinal center response, even after long-lasting allergen challenges. The research revealed that the antigen-binding properties of individual B-cell receptors determine differential IgE hypermutation and IgE versus IgG1 production on the level of single B-cell clones.
MUCOSAL IMMUNOLOGY
(2022)
Article
Immunology
Sayaka Ishihara, Tsuyoshi Sato, Risa Sugioka, Ryota Miwa, Haruka Saito, Ryota Sato, Hidehiro Fukuyama, Akihiko Nakajima, Satoshi Sawai, Ai Kotani, Koko Katagiri
Summary: The regulation of integrins by Rap1 is essential for lymphocyte recirculation, as demonstrated in mice with B-cell-specific Rap1a/b double knockouts. This deficiency leads to a significant decrease in B cells in lymph nodes and impaired germinal center formation and antibody production upon immunization. Additionally, Rap1 deficiency affects the positioning of B cells and their interaction with stromal cells, influencing humoral responses and B-1a cell generation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Xin Zhang, Mengjun Zou, Yue Liang, Yonghong Yang, Lina Jing, Minghui Sun, Zhilin Dong, Xinyuan Zhang, Huabao Xiong, Guanjun Dong
Summary: Arctigenin can regulate the differentiation of germinal center B cells in systemic lupus erythematosus (SLE) by inhibiting the IFN-I signaling pathway, leading to the alleviation of disease progression.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Yijang Xu, Hang Zhou, Ginell Post, Hong Zan, Paolo Casali
Summary: The study demonstrates that Rad52 mediates IgD CSR through a microhomology-based DNA repair pathway, leading to the expression of IgD in B cells.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Kathleen Santamaria, Fabienne Desmots, Simon Leonard, Gersende Caron, Marion Haas, Celine Delaloy, Fabrice Chatonnet, Delphine Rossille, Amandine Pignarre, Celine Monvoisin, Marine Seffals, Claire Lamaison, Michel Cogne, Karin Tarte, Thierry Fest
Summary: The expression of CD23 marker plays a crucial role in the differentiation of human LZ B-GC cells, as CD23 expression is restricted to the GC LZ. CD23-negative LZ B-GC cells can differentiate into plasmablasts, while cells expressing CD23 are unable to complete this differentiation process. Analysis indicates that the process of plasma cell differentiation involves a series of gene expression changes, including a transient MYC gene expression supporting B cell proliferation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ashton K. Shiraz, Eric J. Panther, Christopher M. Reilly
Summary: B lymphocytes play an important role in autoimmune disorders through their production of autoantibodies and secretion of cytokines. However, the association between B-cell metabolism and autoimmune dysfunction is not well understood.
Article
Immunology
Paolo Casali, Shili Li, Grecia Morales, Cassidy C. Daw, Daniel P. Chupp, Amanda D. Fisher, Hong Zan
Summary: IgA is the dominant antibody isotype in intestinal mucosae and dysregulation of its production can lead to diseases. MiR-146a plays a role in modulating CSR to IgA by targeting Smad2, Smad3, and Smad4 in B cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Hongchang Zhao, Stella R. Hartono, Kirtney Mae Flores de Vera, Zheyuan Yu, Krishni Satchi, Tracy Zhao, Roger Sciammas, Lionel Sanz, Frederic Chedin, Jacqueline Barlow, Michela Di Virgilio
Summary: Class switch recombination is a crucial process for generating distinct antibody isotypes, and defects in this process are associated with autoimmune disorders and lymphoma genesis. In this study, we found that cells lacking two enzymes involved in removing R loops exhibited increased R loop formation and genome instability at the immunoglobulin heavy chain locus. However, this did not affect transcriptional activity, AID recruitment, or class switch recombination efficiency. Our findings suggest that senataxin and RNase H2 act together in removing R loops, promoting efficient repair and suppressing AID-dependent genome instability and insertional mutagenesis.
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
Medicine, General & Internal
Verena Sengpiel, Ylva Carlsson, Jan-Ake Liljeqvist, Anders Elfvin, Ing-Marie Fyhr, Anna Lundgren, Kristina Nystrom, Mats Bemark, Magnus Gisslen, Johan Ringlander
Summary: This study reports the first case of reinfection with SARS-CoV-2 during pregnancy. Although the mother lacked detectable antibodies 2 months after the first infection, both mother and baby had IgG antibodies at delivery. Infection did not result in any adverse pregnancy outcome.
CLINICAL CASE REPORTS
(2022)
Article
Immunology
Ajibola Omokanye, Li Ching Ong, Cristina Lebrero-Fernandez, Valentina Bernasconi, Karin Schon, Anneli Stromberg, Mats Bemark, Xavier Saelens, Paulo Czarnewski, Nils Lycke
Summary: Intranasal immunization with CTA1-3M2e-DD stimulates M2e-specific Th17 Trm cells, which provide strong protection against influenza virus infection and tissue injury. Single-cell RNAseq analysis reveals functional diversity of these Trm cells in the lung, and the same TCR clonotype can differentiate into different subclusters with distinct functions. These findings have important implications for vaccine development against respiratory virus infections.
MUCOSAL IMMUNOLOGY
(2022)
Article
Immunology
Jacqueline H. Y. Siu, Michael J. Pitcher, Thomas J. Tull, Rebekah L. Velounias, William Guesdon, Lucia Montorsi, Krishnaa T. Mahbubani, Richard Ellis, Pawan Dhami, Katrina Todd, Ulrich D. Kadolsky, Michelle Kleeman, David P. D'Cruz, Kourosh Saeb-Parsy, Mats Bemark, Gavin J. Pettigrew, Jo Spencer
Summary: This study provides a deep analysis of B cells in lymphoid tissues and blood of deceased organ donors, leading to the identification of two subsets of marginal zone B (MZB) cells with distinct features and roles in immune response and pathology, emphasizing the importance of considering MZB cell heterogeneity in studying human B cell responses.
SCIENCE IMMUNOLOGY
(2022)
Article
Cell Biology
Kathrin Pfeifer, Georg Wolfstetter, Vimala Anthonydhason, Tafheem Masudi, Badrul Arefin, Mats Bemark, Patricia Mendoza-Garcia, Ruth H. Palmer
Summary: This study investigated the relationship between ALK mutations and neuroblastoma using a fruit fly model. The researchers found that ALK mutations enhanced Alk signaling and caused hyperplasia by regulating apoptosis levels. Using single-cell RNA sequencing, they also identified the impact of ALK mutations on temporal fate specification in neuronal lineages.
DISEASE MODELS & MECHANISMS
(2022)
Article
Immunology
Inta Gribonika, Anneli Stromberg, Cristina Lebrero-Fernandez, Karin Schon, James Moon, Mats Bemark, Nils Lycke
Summary: This study found that T(H)17 cells in the intestinal immune system are responsive to both pathogenic and commensal bacteria, but their plasticity to convert into T-FH cells is not a major contributor to gut IgA responses. Two mouse models of T(H)17 deficiency confirmed that gut IgA responses to oral immunization do not require T(H)17 cells.
SCIENCE IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Richard Ainsworth, Deepa Hammaker, Gyrid Nygaard, Cecilia Ansalone, Camilla Machado, Kai Zhang, Lina Zheng, Lucy Carrillo, Andre Wildberg, Amanda Kuhs, Mattias N. D. Svensson, David L. Boyle, Gary S. Firestein, Wei Wang
Summary: This study characterizes clusters of RA cell lines with distinctive TF biology by integrating transcriptomic and epigenomic data and validates the predicted differences.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Malin C. Erlandsson, Seval Erdogan, Caroline Wasen, Karin M. E. Andersson, Sofia T. Silfversward, Rille Pullerits, Mats Bemark, Maria Bokarewa
Summary: This study demonstrates the important role of IGF1R in preventing autoimmunity both in experimental models and in patient material, and raises awareness of potential immune tolerance breakdown during therapeutic IGF1R targeting.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Malin C. Erlandsson, Mahomud Tuameh, Elin Jukic Huduti, Sofia T. Silfversward, Rille Pullerits, Maria Bokarewa
Summary: This study found a low frequency of DMab in RA patients, but DMab showed specificity for the presence of DM. Men had a higher risk of developing DM in RA patients. DM significantly increased the risk of mortality in RA patients.
Article
Medicine, Research & Experimental
Lydia Scharf, Hannes Axelsson, Aikaterini Emmanouilidi, Nimitha R. Mathew, Daniel J. Sheward, Susannah Leach, Pauline Isakson, Ilya V. Smirnov, Emelie Marklund, Nicolae Miron, Lars-Magnus Andersson, Magnus Gisslen, Ben Murrell, Anna Lundgren, Mats Bemark, Davide Angeletti
Summary: Understanding the persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial. This study found that the proportion of Spike receptor binding domain-specific memory B cells increased after infection, while other Spike- and Nucleocapsid-specific B cells remained constant. Affinity maturation of antigen-specific cells continued and was not significantly increased after vaccination. Some clones detected during hospitalization persisted as memory B cells for up to 1 year and monoclonal antibodies derived from these clones showed increased binding and neutralization breadth against viral variants.
Article
Immunology
Anna Lundgren, Susannah Leach, Hannes Axelsson, Pauline Isakson, Kristina Nystrom, Lydia Scharf, Bengt A. Andersson, Nicolae Miron, Emelie Marklund, Lars-Magnus Andersson, Magnus Gisslen, Davide Angeletti, Mats Bemark
Summary: Antigen-specific class-switched antibodies can be detected in the serum of non-vaccinated individuals infected with SARS-CoV-2, indicating early B-cell activation. Plasmablasts during infection produce IgA1, IgG1, and IgM, and show reactivity to spike and nucleocapsid proteins of the Wuhan strain as well as later variants.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Letter
Immunology
Jo Spencer, Thomas J. Tull, Mats Bemark
IMMUNOLOGY LETTERS
(2023)
Review
Gastroenterology & Hepatology
Jo Spencer, Mats Bemark
Summary: This Review provides a comprehensive overview of the role of human intestinal B cells in maintaining gut homeostasis and their involvement in intestinal and systemic inflammatory diseases. The activation and maturation of B cells lead to the production of IgA-secreting plasma cells and their niches in the gut support systemic immune cell specialization. The gut environment is crucial for the development and maturation of splenic B cell subsets and plays a significant role in the abundance of germinal centre microenvironments.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Cell Biology
Vanda Friman, Isabella Quinti, Alexey N. Davydov, Mikhail Shugay, Chiara Farroni, Erik Engstrom, Shirin Pour Akaber, Sabina Barresi, Ahmed Mohamed, Federica Pulvirenti, Cinzia Milito, Guido Granata, Ezio Giorda, Sara Ahlstrom, Johanna Karlsson, Emiliano Marasco, Valentina Marcellini, Chiara Bocci, Simona Cascioli, Marco Scarsella, Ganesh Phad, Andreas Tilevik, Marco Tartaglia, Mats Bemark, Dmitriy M. Chudakov, Rita Carsetti, Ola Grimsholm
Summary: CVID is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but the mechanisms of B cell central and peripheral selection in CVID are not fully understood. This study found that central tolerance is increased in transitional B cells from CVID patients with autoimmune manifestations, while the selection pressure in germinal center on CD27bright memory B cells is decreased. Naive B cells in CVID patients also showed poor activation and induction of mismatch repair genes. These findings suggest defective peripheral selection in CVID patients with autoimmune manifestations, which may contribute to the development of autoimmunity.
Article
Environmental Sciences
Axel G. Andersson, Anna Lundgren, Yiyi Xu, Christel Nielsen, Christian H. Lindh, Daniela Pineda, Julia Cederlund, Elisavet Pataridou, Sandra Sogaard Tottenborg, Kajsa Ugelvig Petersen, Tony Fletcher, Martin Lagging, Mats Bemark, Kristina Jakobsson, Ying Li
Summary: This study aimed to evaluate the association between PFAS exposure levels and antibody responses after SARS-CoV-2 vaccination in adults. The results showed no negative correlation between PFAS exposure and antibody levels 5 weeks and 6 months after COVID-19 vaccination.
ENVIRONMENTAL HEALTH PERSPECTIVES
(2023)
Editorial Material
Oncology
Sahil Jain, Mats Bemark, Jo Spencer
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)