ArticleFrontiers in immunology2020
Multiscale Modeling of Germinal Center Recapitulates the Temporal Transition From Memory B Cells to Plasma Cells Differentiation as Regulated by Antigen Affinity-Based Tfh Cell Help.
Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Integrative agent-based modeling of cutaneous lupus: single-cell benchmarking and in silico evaluation of B-cell therapies.Briefings in bioinformatics · 2026Article
- Phased fragility and stability of non-genetic B cell states in the germinal center accelerate the genetic evolution of antibodies.Cell systems · 2026Article
- Article
- Simvastatin Combined with CpG Enhances the Immunogenicity of the H9N2 Inactivated Vaccine.Veterinary sciences · 2025Article
- B cell immunity and therapeutic opportunities in brain metastases.Frontiers in immunology · 2025Review
- ENCORE: a practical implementation to improve reproducibility and transparency of computational research.Nature communications · 2024Article
- A multiscale spatial modeling framework for the germinal center response.Frontiers in immunology · 2024Article
- Stochastic modeling of a gene regulatory network driving B cell development in germinal centers.PloS one · 2024Article
- Understanding repertoire sequencing data through a multiscale computational model of the germinal center.NPJ systems biology and applications · 2023Article
- High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies.Cells · 2022Article
- Termination of CD40L co-stimulation promotes human B cell differentiation into antibody-secreting cells.European journal of immunology · 2022Article
- From affinity selection to kinetic selection in Germinal Centre modelling.PLoS computational biology · 2022Article
- Investigating the Mechanism of Germinal Center Shutdown.Frontiers in immunology · 2022Article
- Sterilizing Immunity against COVID-19: Developing Helper T cells I and II activating vaccines is imperative.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Coupled Antigen and BLIMP1 Asymmetric Division With a Large Segregation Between Daughter Cells Recapitulates the Temporal Transition From Memory B Cells to Plasma Cells and a DZ-to-LZ Ratio in the Germinal Center.Frontiers in immunology · 2021Article
- Advances in understanding the formation and fate of B-cell memory in response to immunization or infection.Oxford open immunology · 2021Review
- System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation.Frontiers in immunology · 2021Review
- Compartments and Connections Within the Germinal Center.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Germinal centers play a key role in the adaptive immune system since they are able to produce memory B cells and plasma cells that produce high affinity antibodies for an effective immune protection. The mechanisms underlying cell-fate decisions are not well understood but asymmetric division of antigen, B-cell receptor affinity, interactions between B-cells and T follicular helper cells (triggering CD40 signaling), and regulatory interactions of transcription factors have all been proposed to play a role. In addition, a temporal switch from memory B-cell to plasma cell differentiation during the germinal center reaction has been shown. To investigate if antigen affinity-based Tfh cell help recapitulates the temporal switch we implemented a multiscale model that integrates cellular interactions with a core gene regulatory network comprising BCL6, IRF4, and BLIMP1. Using this model we show that affinity-based CD40 signaling in combination with asymmetric division of B-cells result in switch from memory B-cell to plasma cell generation during the course of the germinal center reaction. We also show that cell fate division is unlikely to be (solely) based on asymmetric division of Ag but that BLIMP1 is a more important factor. Altogether, our model enables to test the influence of molecular modulations of the CD40 signaling pathway on the production of germinal center output cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.