title: Global transcriptome analysis and enhancer landscape of human primary T follicular helper and T effector lymphocytes.
abstract: T follicular helper (Tfh) cells are a subset of CD4(+) T helper cells that migrate into germinal centers and promote B-cell maturation into memory B and plasma cells. Tfh cells are necessary for promotion of protective humoral immunity following pathogen challenge, but when aberrantly regulated, drive pathogenic antibody formation in autoimmunity and undergo neoplastic transformation in angioimmunoblastic T-cell lymphoma and other primary cutaneous T-cell lymphomas. Limited information is available on the expression and regulation of genes in human Tfh cells. Using a fluorescence-activated cell sorting-based strategy, we obtained primary Tfh and non-Tfh T effector cells from tonsils and prepared genome-wide maps of active, intermediate, and poised enhancers determined by chromatin immunoprecipitation-sequencing, with parallel transcriptome analyses determined by RNA sequencing. Tfh cell enhancers were enriched near genes highly expressed in lymphoid cells or involved in lymphoid cell function, with many mapping to sites previously associated with autoimmune disease in genome-wide association studies. A group of active enhancers unique to Tfh cells associated with differentially expressed genes was identified. Fragments from these regions directed expression in reporter gene assays. These data provide a significant resource for studies of T lymphocyte development and differentiation and normal and perturbed Tfh cell function.
authors.affiliation: Rheumatology Section, Department of Internal Medicine.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Weinstein
authors.affiliation: Department of Pediatrics.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Lezon-Geyda
authors.affiliation: Department of Pediatrics.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Maksimova
authors.affiliation: Department of Pediatrics.
authors.forename: Samuel
authors.initials: S
authors.lastname: Craft
authors.affiliation: Department of Pediatrics.
authors.forename: Yaoping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics.
authors.forename: Mack
authors.initials: M
authors.lastname: Su
authors.affiliation: Department of Pediatrics.
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Schulz
authors.affiliation: Rheumatology Section, Department of Internal Medicine, Department of Immunobiology, and.
authors.forename: Joseph
authors.initials: J
authors.lastname: Craft
authors.affiliation: Department of Pediatrics, Departments of Pathology and Genetics, Yale School of Medicine, New Haven, CT.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Gallagher
mesh_terms: D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005434:Flow Cytometry; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D014066:Palatine Tonsil / Q000166:cytology; D061251:Primary Cell Culture; D017423:Sequence Analysis, RNA; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000378:metabolism*; D059467:Transcriptome / Q000235:genetics*