#GerminalCenter

'Here, we showed that IL-4 cytokine signaling in GC B cells directly downregulated the transcription factor BCL6 via negative autoregulation to release cells from the GC program and to promote MBC formation.'
#GerminalCenter
#Immunology

https://www.cell.com/immunity/abstract/S1074-7613(24)00094-3

"Our experiments confirm that GCs support the side-by-side maturation of B cells with very different BCR affinities and reveal that cells from across a wide antibody affinity spectrum generate PCs. We propose that this outcome reflects imprecise discrimination for antibody affinity by GC B cells in such settings, with the result being PC populations that approximately mirror the maturation pathways from which they develop. This provides the evolutionary benefit of seeding diverse serum antibody responses."
#Immunology #GerminalCenter

https://www.cell.com/cell/fulltext/S0092-8674(23)01173-X#%20

"Highlighting the role of repeated immune responses, our results confirm the role of REL in the germinal center reaction and provide evidence supporting the fact that genetic deregulation of c-Rel expression is most likely a primary event in the aggressive transformation of GC B-cells."
#Preprint #GerminalCenter #Immunology

https://www.biorxiv.org/content/10.1101/2023.10.10.561773v1

"We review how both TFH and TFR cells express helper and repressor factors that coordinately regulate the Ab response and how the line between these two subsets is less clear than initially thought."
#Immunology #GerminalCenter

https://journals.aai.org/jimmunol/article-abstract/211/1/15/263866/Nonbinary-Roles-for-T-Follicular-Helper-Cells-and?redirectedFrom=fulltext

'We found that the follicular dendritic cell network was smaller in aged mice. Furthermore, the TFH cells that are normally localized within the light zone were instead dispersed throughout the GC in aged mice (Fig. 1), owing to enhanced expression of CXCR4 (a CXCL12 receptor) that directed the TFH cells to the CXCL12-rich dark zone.'
#Immunology #GerminalCenter

https://www.nature.com/articles/s41590-023-01520-2

'We find that DYRK1A is essential for protection from viral infection through CSR, mediated by phosphorylation of MSH6. Furthermore, DYRK1A regulates Germinal Center seeding and subsequent effective clonal expansion through the attenuation of cell-cycle progression.'

#Immunology #GerminalCenter

https://www.nature.com/articles/s41467-023-37205-5

'Tingible body macrophages (TBMs) are tasked with apoptotic cell clearance to prevent secondary necrosis and autoimmune activation by intracellular self antigens. We show by multiple redundant and complementary methods that TBMs derive from a lymph node-resident, CD169-lineage, CSF1R-blockade-resistant precursor that is prepositioned in the follicle.'

#immunology #Macrophage #Apoptosis #GerminalCenter

https://www.cell.com/cell/fulltext/S0092-8674(23)00106-X

"Vaccines that resulted in speedy delivery of antigens to follicles preserved intact antigen and generated better antibody responses. These findings may have implications for the design of vaccines against difficult to neutralize or genetically variable pathogens"

#Immunology #ImmunologicalMemory #Antibody #GerminalCenter #Bcells #Vaccine

https://www.science.org/doi/10.1126/science.abn8934

"During systemic Salmonella Typhimurium (STm) infection germinal centers are absent, whereas extensive extrafollicular switched antibody responses are maintained. The mechanisms that underpin the absence of GC formation are incompletely understood. Here, we show that STm-induces a reversible disruption of niches within the splenic microenvironment, including the T and B cell compartments and the marginal zone."

#GerminalCenter #Salmonella #Immunology #Infection #HostPathogen #Preprint

cc @mucida @kevinng @BrodskyLab @victoralab

https://www.biorxiv.org/content/10.1101/2022.12.11.519997v1

'The mechanism underlying these findings was examined in experiments in mice that showed that germinal centers (GCs) formed in the presence of the same antibodies were dominated by low-affinity B cells. Our results indicate that pre-existing high-affinity antibodies bias GC and memory B cell selection by two distinct mechanisms: (1) by lowering the activation threshold for B cells thereby permitting abundant lower-affinity clones to participate in the immune response, and (2) through direct masking of their cognate epitopes. This may in part explain the shifting target profile of memory antibodies elicited by booster vaccinations'

#Immunology #Bcells #GerminalCenter #Covid19

https://www.nature.com/articles/s41586-022-05609-w