{"doi":"10.1126/sciimmunol.adf2248","title":"The transcription factor Mef2d regulates B:T synapse–dependent GC-T <sub>FH</sub> differentiation and IL-21–mediated humoral immunity","abstract":"Communication between CD4 T cells and cognate B cells is key for the former to fully mature into germinal center–T follicular helper (GC-T FH ) cells and for the latter to mount a CD4 T cell–dependent humoral immune response. Although this interaction occurs in a B:T synapse–dependent manner, how CD4 T cells transcriptionally regulate B:T synapse formation remains largely unknown. Here, we report that Mef2d, an isoform of the myocyte enhancer factor 2 (Mef2) transcription factor family, is a critical regulator of this process. In CD4 T cells, Mef2d negatively regulates expression of Sh2d1a , which encodes SLAM-associated protein (SAP), a critical regulator of B:T synapses. We found that Mef2d regulates Sh2d1a expression via DNA binding–dependent transcriptional repression, inhibiting SAP-dependent B:T synapse formation and preventing antigen-specific CD4 T cells from differentiating into GC-T FH cells. Mef2d also impeded IL-21 production by CD4 T cells, an important B cell help signaling molecule, via direct repression of the Il21 gene. In contrast, CD4 T cell–specific disruption of Mef2d led to a substantial increase in GC-T FH differentiation in response to protein immunization, concurrent with enhanced SAP expression. MEF2D mRNA expression inversely correlates with human systemic lupus erythematosus (SLE) patient autoimmune parameters, including circulating T FH –like cell frequencies, autoantibodies, and SLEDAI scores. These findings highlight Mef2d as a pivotal rheostat in CD4 T cells for controlling GC formation and antibody production by B cells.","journal":"Science Immunology","year":2023,"id":336084,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1066481,"name":"Jeein Oh","orcid":"0000-0002-7075-7653","position":1,"is_corresponding":false},{"id":1066482,"name":"Soohan Jung","orcid":"0000-0003-3572-1126","position":2,"is_corresponding":false},{"id":1066483,"name":"Chan Johng Kim","orcid":"0000-0002-7256-0205","position":3,"is_corresponding":false},{"id":104940,"name":"Jinyong Choi","orcid":"0000-0003-2474-2837","position":4,"is_corresponding":false},{"id":666395,"name":"Yoon Kyung Jeon","orcid":"0000-0001-8466-9681","position":5,"is_corresponding":false},{"id":1066484,"name":"Hyun Jik Kim","orcid":"0000-0001-8631-928X","position":6,"is_corresponding":false},{"id":242060,"name":"Ji-Won Kim","orcid":"0000-0002-2827-0884","position":7,"is_corresponding":false},{"id":250952,"name":"Chang‐Hee Suh","orcid":"0000-0001-6156-393X","position":8,"is_corresponding":false},{"id":1066485,"name":"Yoontae Lee","orcid":"0000-0002-6810-3087","position":9,"is_corresponding":false},{"id":1066486,"name":"Sin‐Hyeog Im","orcid":"0000-0002-3173-1856","position":10,"is_corresponding":false},{"id":103780,"name":"Shane Crotty","orcid":"0000-0002-6484-6262","position":11,"is_corresponding":false},{"id":1066487,"name":"Youn Soo Choi","orcid":"0000-0001-6291-6178","position":12,"is_corresponding":false},{"id":1066480,"name":"Ye-Ji Kim","orcid":"0000-0001-7155-9635","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T01:10:17.243221Z","pmid":"36961907","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":[]}