{"doi":"10.1093/jimmun/vkaf283.142","title":"Tfh cell regulation and the impact on B cells in viral infection 2194","abstract":"Abstract Description Host immunity to pathogens is shaped by crosstalk between innate and adaptive cells. NK cells are innate immune cells that can modulate adaptive responses. Following infection, NK cells migrate into the T zone and suppress T follicular helper (Tfh) cells. This inhibits Tfh cell migration into the B cell follicle and their promotion of antibody responses by germinal center (GC) and age-associated B cells (ABCs). We assessed the cellular and molecular mechanisms underlying NK–mediated suppression of Tfh and B cell responses. We utilize antibody depletion and a novel NK cell knockout model to examine NK-Tfh cell interactions during acute LCMV infection. We show that the absence of NK cells results in the expansion of Tfh cells but not Th1 cells following infection. We found that ICOS, a critical activation receptor for Tfh cell development, is more highly expressed in Tfh cells without NK cells. Transcriptional analysis of Tfh cells demonstrated increased upregulation of genes involved in activation without NK cells. NK cells had a temporal upregulation of ICOS ligand (ICOSL) during early Tfh cell development, indicating the interaction between NK and Tfh cells is mediated by ICOS/ICOSL. Moreover, in the absence of NK cells, the frequency of GC B cells and anti-LCMV antibody titers were similar, but ABCs were expanded. These data indicate that NK cells regulate overactivated Tfh cells in viral infection through ICOS-ICOSL interactions, thus altering the ABC response. Funding Sources Supported by NIH R01 AR073912 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)","journal":"The Journal of Immunology","year":2025,"id":582444,"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":0.9639,"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":1494503,"name":"Eric K Tang","orcid":null,"position":1,"is_corresponding":false},{"id":300713,"name":"Aimee M. Beaulieu","orcid":"0000-0002-7301-0002","position":2,"is_corresponding":false},{"id":227274,"name":"Jason S. Weinstein","orcid":"0000-0001-9918-2817","position":3,"is_corresponding":false},{"id":1282106,"name":"Eden S Hirsch","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:55.657290Z","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":[]}