{"doi":"10.3389/fimmu.2021.635748","title":"Identification of a Sensitive Human Immunological Target of Aryl Hydrocarbon Receptor Activation: CD5+ Innate-Like B Cells","abstract":"Xenobiotic-mediated activation of the aryl hydrocarbon receptor (AHR) is immunotoxic in a number of immune cell types, with the B cell being a well-established sensitive target. Recent advances have provided evidence that the B cell repertoire is a heterogeneous population, with subpopulations exhibiting vastly different cellular and functional phenotypes. Recent work from our laboratory identified the T cell specific kinase lck as being differentially regulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which is a potent activator of AHR. While LCK is primarily expressed in T cells, a subset of CD5 + B cells also express LCK. CD5 positivity describes a broad class of B lymphocytes termed innate-like B cells (ILBs) that are critical mediators of innate immunity through constitutive secretion of polyvalent natural immunoglobulin M (IgM). We hypothesized that CD5 + ILBs may be sensitive to AHR-mediated immunotoxicity. Indeed, when CD5 + B cells were isolated from the CD19 + pool and treated with TCDD, they showed increased suppression of the CD40 ligand-induced IgM response compared to CD5 - B cells. Further, characterization of the CD5 + population indicated increased basal expression of AHR , AHR repressor ( AHRR ), and cytochrome p450 family 1 member a1 ( CYP1A1 ). Indeed the levels of AHR-mediated suppression of the IgM response from individual donors strongly correlated with the percentage of the B cell pool that was CD5 + , suggesting that CD5 + B cells are more sensitive to AHR-mediated impairment. Together these data highlight the sensitive nature of CD5 + ILBs to AHR activation and provide insight into mechanisms associated with AHR activation in human B cells.","journal":"Frontiers in Immunology","year":2021,"id":197810,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":771898,"name":"Jiajun Zhou","orcid":"0000-0003-1135-4536","position":1,"is_corresponding":false},{"id":666082,"name":"Robert B. Crawford","orcid":"0000-0002-8507-1021","position":2,"is_corresponding":false},{"id":666083,"name":"Norbert E. Kaminski","orcid":"0000-0002-2144-428X","position":3,"is_corresponding":false},{"id":593507,"name":"Lance K. Blevins","orcid":"0000-0002-8911-8843","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-18T23:50:23.532351Z","pmid":"33936048","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":[]}