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Signals that influence T follicular helper cell differentiation and function

Linterman, Michelle; Garcia De Vinuesa, Maria Carola

Description

Follicular helper T cells have recently emerged as a separate CD4 + T helper lineage specialised in provision of help to B cells. They develop independently from Th1, Th2 and Th17 cells and are critical for humoral immunity, including the generation of long-lived and high affinity plasma cells and memory cells crucial for long-term protection against infections. A stepwise differentiation programme has emerged in which T cell receptor (TCR) signalling strength, CD28-mediated costimulation, B...[Show more]

dc.contributor.authorLinterman, Michelle
dc.contributor.authorGarcia De Vinuesa, Maria Carola
dc.date.accessioned2015-12-10T23:12:43Z
dc.identifier.issn1863-2297
dc.identifier.urihttp://hdl.handle.net/1885/64100
dc.description.abstractFollicular helper T cells have recently emerged as a separate CD4 + T helper lineage specialised in provision of help to B cells. They develop independently from Th1, Th2 and Th17 cells and are critical for humoral immunity, including the generation of long-lived and high affinity plasma cells and memory cells crucial for long-term protection against infections. A stepwise differentiation programme has emerged in which T cell receptor (TCR) signalling strength, CD28-mediated costimulation, B cell-derived inducible costimulator ligand signals, induction of c-maf and actions of cytokines, including interleukin (IL)-6 and IL-21, lead to upregulation of the transcriptional repressor B cell lymphoma 6 (Bcl-6) that drives T follicular helper (Tfh) cell differentiation. Bcl-6 turns on a repression programme that targets Blimp-1, transcriptional regulators of other helper lineages and microRNAs. Their concerted actions modulate expression of chemokine receptors, surface molecules and cytokines critical for follicular homing and B cell helper functions. Here, we review the nature of Tfh cells providing help to B cells during the two phases of B cell activation that occur in the outer T zone and, for some B cells, in germinal centres (GC). Recent insights into the signalling events that drive terminal differentiation of Tfh cells critical for selecting somatically mutated GC B cells and the consequences of Tfh dysregulation for immunodeficiency and autoimmune pathology are discussed.
dc.publisherSpringer
dc.sourceSeminars in Immunopathology
dc.subjectKeywords: B lymphocyte induced maturation protein 1; B7 antigen; CD134 antigen; CD150 antigen; CD28 antigen; CD30 antigen; CD4 antigen; CD86 antigen; chemokine; chemokine receptor CCR7; chemokine receptor CXCR5; cytokine; Fas antigen; interleukin 21; interleukin 21 Bcl-6; CD28; Costimulation; ICOS; IL-21; SAP (Sh2d1a); T follicular helper cells (Tfh); TCR signalling
dc.titleSignals that influence T follicular helper cell differentiation and function
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume32
dc.date.issued2010
local.identifier.absfor110704 - Cellular Immunology
local.identifier.ariespublicationf2965xPUB888
local.type.statusPublished Version
local.contributor.affiliationLinterman, Michelle A., Cambridge Institute for Medical Research
local.contributor.affiliationGarcia De Vinuesa, Maria Carola, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue2
local.bibliographicCitation.startpage183
local.bibliographicCitation.lastpage196
local.identifier.doi10.1007/s00281-009-0194-z
local.identifier.absseo920108 - Immune System and Allergy
dc.date.updated2016-02-24T08:33:41Z
local.identifier.scopusID2-s2.0-77955487468
local.identifier.thomsonID000277556700010
CollectionsANU Research Publications

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