Computational Modeling of Germinal Center Response

The germinal center response (GCR) is a critical event in adaptive humoral immunity involving activation and differentiation of B cells. Many environmental pollutants may disrupt the B cell response. GCR is a T cell-dependent process, involving cell-to-cell interactions with spatial complexity. The formation of GC requires activated B cells to migrate between the dark and light zones for multiple cycles, during which they undergo clonal expansion, somatic hypermutation, and apoptosis. This spatial behavior is crucial to the formation of long-lived plasma cells that secrete high-affinity immunoglobulins. The process is underpinned by a complex gene network responding to chemoattracting signals and cytokines from T cells and follicular dendritic cells (FDC). Here I present a mathematical model of GCR using the CompuCell3D platform. Tellurium is used to simulate the intracellular gene network. The model captures the key events in GCR, including B cell proliferation and somatic hypermutation in the dark zone, migration of B cells to the light zone where they interact with FDC and T cells to check for antibody affinity and make decisions for apoptosis, survival or returning to the dark zone. The migration of B cells within GC is driven by the gradients of chemoattractants CXCL12 and CXCL13, and the receptors CXCR4 and CXCR5, whose expression, along with cell proliferation, is regulated by the interaction with FDC and T cells. Our simulations predict the morphological and functional consequences of GCR when key events are disrupted, such as inhibition of B cell proliferation by environmental immunotoxicant polychlorinated dibenzo-p-dioxins. In summary, the virtual GCR model has the potential to be used to better understand the mechanism of GCR, its disruption and enhancement by environmental and pharmaceutical chemicals. Moderator: James A. Glazier, PhD, Indiana University, Bloomington To learn more see: Mu, Derek P., Christopher D. Scharer, Norbert E. Kaminski, and Qiang Zhang. "A multiscale spatial modeling framework for the germinal center response." Frontiers in Immunology 15 (2024): 1377303. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1377303/full *Contents* 00:00 - Introduction 07:18 - Qiang Zhang: Computational Modeling of Germinal Center Response 51:10 - Discussion To view the slides in this video, visit: https://drive.google.com/file/d/1gu_qZlihJAam0aZcdM3Jat930Vxs_4zg/ If you found this video useful, please check out our other videos on computational modeling, infection and immunology: https://tinyurl.com/GLIMPRINTVideos Please consider joining our IMAG/MSM WG on Multiscale Modeling and Viral Pandemics: https://www.imagwiki.nibib.nih.gov/content/msm-viral-pandemics-meetings