Evidence map›Paper›PMID 38881901›Full record

ArticleFrontiers in immunology2024

A multiscale spatial modeling framework for the germinal center response.

Derek P Mu, Christopher D Scharer, Norbert E Kaminski, Qiang Zhang

Abstract read
In one paragraph

Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Derek P MuMontgomery Blair High School, Silver Spring, MD, United States.
Christopher D ScharerDepartment of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA, United States.
Norbert E KaminskiDepartment of Pharmacology & Toxicology, Institute for Integrative Toxicology, Center for Research on Ingredient Safety, Michigan State University, East Lansing, MI, United States.
Qiang ZhangGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, United States.

Funding

VOLATILE ORGANIC CONTAMINANTS--QUANTIFYING THEIR MOVEMENT IN THE UNSATURATED ZONEP42ES004911 · NIEHS · MICHIGAN STATE UNIVERSITY · PI Brian P. Johnson · 1989 to 2026
$64.9M
NIEHS NIH HHS P42 ES004911
6 · The paper itself

Abstract

The germinal center response or reaction (GCR) is a hallmark event of adaptive humoral immunity. Unfolding in the B cell follicles of the secondary lymphoid organs, a GC culminates in the production of high-affinity antibody-secreting plasma cells along with memory B cells. By interacting with follicular dendritic cells (FDC) and T follicular helper (Tfh) cells, GC B cells exhibit complex spatiotemporal dynamics. Driving the B cell dynamics are the intracellular signal transduction and gene regulatory network that responds to cell surface signaling molecules, cytokines, and chemokines. As our knowledge of the GC continues to expand in depth and in scope, mathematical modeling has become an important tool to help disentangle the intricacy of the GCR and inform novel mechanistic and clinical insights. While the GC has been modeled at different granularities, a multiscale spatial simulation framework - integrating molecular, cellular, and tissue-level responses - is still rare. Here, we report our recent progress toward this end with a hybrid stochastic GC framework developed on the Cellular Potts Model-based CompuCell3D platform. Tellurium is used to simulate the B cell intracellular molecular network comprising NF-κB, FOXO1, MYC, AP4, CXCR4, and BLIMP1 that responds to B cell receptor (BCR) and CD40-mediated signaling. The molecular outputs of the network drive the spatiotemporal behaviors of B cells, including cyclic migration between the dark zone (DZ) and light zone (LZ) via chemotaxis; clonal proliferative bursts, somatic hypermutation, and DNA damage-induced apoptosis in the DZ; and positive selection, apoptosis via a death timer, and emergence of plasma cells in the LZ. Our simulations are able to recapitulate key molecular, cellular, and morphological GC events, including B cell population growth, affinity maturation, and clonal dominance. This novel modeling framework provides an open-source, customizable, and multiscale virtual GC simulation platform that enables qualitative and quantitative

Indexed as

B-LymphocytesGerminal CenterAnimalsComputer SimulationHumansImmunity, HumoralModels, ImmunologicalSignal Transductionaffinity maturationB cellschemotaxisdark zonegerminal centerlight zoneproliferative burst

Identifiers

PMID38881901
PMCPMC11179717

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Registered trials

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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 OpenQuestion graph.