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Keywords = asynchronous germinal centers

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17 pages, 3735 KB  
Article
Antibody Mediated Intercommunication of Germinal Centers
by Theinmozhi Arulraj, Sebastian C. Binder and Michael Meyer-Hermann
Cells 2022, 11(22), 3680; https://doi.org/10.3390/cells11223680 - 19 Nov 2022
Cited by 1 | Viewed by 2309
Abstract
Antibody diversification and selection of B cells occur in dynamic structures called germinal centers (GCs). Passively administered soluble antibodies regulate the GC response by masking the antigen displayed on follicular dendritic cells (FDCs). This suggests that GCs might intercommunicate via naturally produced soluble [...] Read more.
Antibody diversification and selection of B cells occur in dynamic structures called germinal centers (GCs). Passively administered soluble antibodies regulate the GC response by masking the antigen displayed on follicular dendritic cells (FDCs). This suggests that GCs might intercommunicate via naturally produced soluble antibodies, but the role of such GC–GC interactions is unknown. In this study, we performed in silico simulations of interacting GCs and predicted that intense interactions by soluble antibodies limit the magnitude and lifetime of GC responses. With asynchronous GC onset, we observed a higher inhibition of late formed GCs compared to early ones. We also predicted that GC–GC interactions can lead to a bias in the epitope recognition even in the presence of equally dominant epitopes due to differences in founder cell composition or initiation timing of GCs. We show that there exists an optimal range for GC–GC interaction strength that facilitates the affinity maturation towards an incoming antigenic variant during an ongoing GC reaction. These findings suggest that GC–GC interactions might be a contributing factor to the unexplained variability seen among individual GCs and a critical factor in the modulation of GC response to antigenic variants during viral infections. Full article
(This article belongs to the Special Issue Emerging Mechanisms in B Cell Activation)
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17 pages, 3256 KB  
Article
In Silico Analysis of the Longevity and Timeline of Individual Germinal Center Reactions in a Primary Immune Response
by Theinmozhi Arulraj, Sebastian C. Binder and Michael Meyer-Hermann
Cells 2021, 10(7), 1736; https://doi.org/10.3390/cells10071736 - 9 Jul 2021
Cited by 1 | Viewed by 3944
Abstract
Germinal centers (GCs) are transient structures in the secondary lymphoid organs, where B cells undergo affinity maturation to produce high affinity memory and plasma cells. The lifetime of GC responses is a critical factor limiting the extent of affinity maturation and efficiency of [...] Read more.
Germinal centers (GCs) are transient structures in the secondary lymphoid organs, where B cells undergo affinity maturation to produce high affinity memory and plasma cells. The lifetime of GC responses is a critical factor limiting the extent of affinity maturation and efficiency of antibody responses. While the average lifetime of overall GC reactions in a lymphoid organ is determined experimentally, the lifetime of individual GCs has not been monitored due to technical difficulties in longitudinal analysis. In silico analysis of the contraction phase of GC responses towards primary immunization with sheep red blood cells suggested that if individual GCs had similar lifetimes, the data would be consistent only when new GCs were formed until a very late phase after immunization. Alternatively, there could be a large variation in the lifetime of individual GCs suggesting that both long and short-lived GCs might exist in the same lymphoid organ. Simulations predicted that such differences in the lifetime of GCs could arise due to variations in antigen availability and founder cell composition. These findings identify the potential factors limiting GC lifetime and contribute to an understanding of overall GC responses from the perspective of individual GCs in a primary immune response. Full article
(This article belongs to the Collection Feature Papers in ‘Cellular Immunology’)
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