{"doi":"10.1093/jimmun/vkaf160","title":"PTEN restricts IL-21R signaling in GC B cells and suppresses their differentiation to plasma cells","abstract":"The germinal center (GC) reaction is essential for generating high-quality humoral memory. Positively selected GC B cells must decide whether to remain in the GC for further affinity maturation or differentiate into memory or plasma cells (PCs). Previously, we identified IL-21R and CD40 signaling as critical promoters of GC B cell effector differentiation. However, the mechanisms regulating the strength of these signals remain unclear. PTEN, a negative regulator of PI3K signaling, is markedly upregulated in GC B cells. To explore the role of PTEN in GC B cell fate decisions, we used a tamoxifen-driven Cre system to delete PTEN in B cells after GC reaction was fully established. We found that PTEN deletion in ongoing GC B cells led to significantly increased differentiation into PCs, while having limited effects on class switching or memory precursor differentiation. These results were further confirmed using a GC B cell transfer system, where wild-type and PTEN-deficient GC B cells were transferred into the same recipient mice. Mechanistically, PTEN deletion or inhibition in established GC B cells resulted in more sustained IL-21R signaling and enhanced CD40 signaling-both known to promote PC differentiation. Interestingly, Peyer's patch GC B cells exhibited higher PTEN levels than de novo GC B cells generated through immunization. Notably, PTEN deficiency selectively expanded GC B cells in Peyer's patches but had no impact on those induced by immunization. These findings reveal previously unrecognized roles for PTEN in regulating GC B cell signaling and limiting their differentiation into PCs.","journal":"The Journal of Immunology","year":2025,"id":534414,"datarank":0.17706632462263217,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.012274481322415697,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.012274481322415697,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9438,"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":855860,"name":"Wenxia Jiang","orcid":"0000-0003-2307-5091","position":1,"is_corresponding":false},{"id":237074,"name":"Laura Conter","orcid":"0000-0002-8528-0528","position":2,"is_corresponding":false},{"id":239075,"name":"Daniel J. Wikenheiser","orcid":null,"position":3,"is_corresponding":false},{"id":237072,"name":"William F. Hawse","orcid":"0000-0001-8371-3345","position":4,"is_corresponding":false},{"id":1417560,"name":"Anandkumar Patel","orcid":null,"position":5,"is_corresponding":false},{"id":1417561,"name":"Weixun Peng","orcid":null,"position":6,"is_corresponding":false},{"id":237080,"name":"Mark J. Shlomchik","orcid":"0000-0002-2152-0959","position":7,"is_corresponding":false},{"id":237071,"name":"Wei Luo","orcid":"0000-0003-2826-1723","position":8,"is_corresponding":false},{"id":1239176,"name":"Alexander R. Maldeney","orcid":null,"position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:47.434742Z","pmid":"40795247","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":[]}