title: CD25(+) Bcl6(low) T follicular helper cells provide help to maturing B cells in germinal centers of human tonsil.
abstract: The majority of CXCR5(+) PD1(+) CD4(+) T follicular helper (Tfh) cells (>90%) are CD25(-) Bcl6(hi) , while a small subpopulation (<10%) are CD25(+) Bcl6(low) but do not express FoxP3 and are not T regulatory cells. We purified T:B-cell conjugates from tonsils and found they were enriched for the CD25(+) Bcl6(low) Tfh-cell subpopulation. In response to IL-2, these CD25(+) Tfh cells increased expression of costimulatory molecules ICOS or OX40, upregulated transcription factor cMaf, produced cytokines IL-21, IL-17, and IL-10, and raised the levels of antiapoptotic protein Bcl2. Conjugates formed with CD25(+) BCl6(low) Tfh cells included B cells expressing higher levels of activation-induced cytidine deaminase (AID), memory marker CD45RO, surface IgG or IgA, and MHC class II compared to B-cell conjugates including CD25(-) Bcl6(hi) Tfh cells. While IL-2 suppresses early Tfh-cell differentiation, Tfh-cell recognition of antigen-presenting B cells and signaling through the T-cell receptor likely triggers expression of the high-affinity IL-2 receptor and responses to IL-2 including downregulation of Bcl6. CD25 expression on Tfh cells and local production of IL-2 in tonsil or lymph node may support B helper T-cell function during later stages of B-cell maturation and the development of immune memory.
authors.affiliation: Institute of Human Virology and Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Haishan
authors.initials: H
authors.lastname: Li
authors.forename: C David
authors.initials: CD
authors.lastname: Pauza
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D014066:Palatine Tonsil / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D051560:Proto-Oncogene Proteins c-bcl-6; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000235:genetics* / Q000276:immunology; D053262:Receptors, OX40 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: C084103:BCL6 protein, human; D016207:Cytokines; D004268:DNA-Binding Proteins; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D007376:Interleukin-2; D051560:Proto-Oncogene Proteins c-bcl-6; D051257:Proto-Oncogene Proteins c-maf; D015375:Receptors, Interleukin-2; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human; D017493:Leukocyte Common Antigens; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: B cells; Germinal centers; IL-2 receptor; Interleukin-2; T follicular helper cell