{"doi":"10.1093/jimmun/vkaf283.449","title":"Mechanisms of inflammasome mediated IL-1β production in germinal center B cells 2543","abstract":"Abstract Description Influenza infected mice with a B cell-specific interleukin-1β (IL-1β) deficiency exhibit significant reduction in germinal center (GC) B cells, T follicular helper cells (TFH), and impaired trafficking of TFH cells into the B cell follicles, delineating a role of B cell-derived IL-1β in the GC reaction. Two signals drive IL-1β production - 1) NFkB mediated pro-IL1β expression and 2) activation of inflammasomes to cleave pro-IL1β into the active IL-1β. Extracellular ATP, ROSs, and ion fluxes within the GC suggest the activation of the NOD-like receptor-3 (NLRP3) inflammasome. We hypothesized that NLRP3 activity mediates IL-1β production in GC B cells. Our data show that GC B cells had significantly higher expression of NLRP3 than non-GC (nGC) and naïve B cells. B cell-specific ablation of NLRP3, but not of other inflammasome sensor proteins, showed significant reductions in GC B cell and TFH cell numbers. Mechanisms underpinning NLRP3 activity, like active caspase-1 (aCasp-1) and caspase-8 (aCasp-8) are upregulated in GC B cells. However, coexpression analysis showed significantly higher coexpression of aCasp-1 with IL-1β compared to aCasp-8 with IL-1β in GC vs. nGC B cells, suggesting aCasp-1 is mediating IL-1β activation. Similar to murine B cells, human activated GC B cells from the palatine tonsils showed IL-1β production, mediated by aCasp-1 and NLRP3 inflammasome activity. Our findings expose novel molecular targets to enhance the GC response, post influenza infection. Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)","journal":"The Journal of Immunology","year":2025,"id":586145,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1500571,"name":"Cainan Riccio-Baum","orcid":null,"position":1,"is_corresponding":false},{"id":1500572,"name":"S Rameeza Allie","orcid":null,"position":2,"is_corresponding":false},{"id":942746,"name":"Juliana Restrepo","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:59:28.666390Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}