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T follicular helper cells in space-time
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Journal Article
T follicular helper cells in space-time
2016
Overview
Key Points
T follicular helper (T
FH
) cells are a phenotypically distinct subset of activated T cells that specializes in promoting germinal centre reactions that support B cell proliferation, somatic hypermutation and class-switch recombination.
T
FH
cell development is regulated by a suite of transcriptional factors in conjunction with the master controller B cell lymphoma 6 (BCL-6).
The classical cytokine-centric 'instructional' paradigm of T helper cell differentiation cannot fully explain how T
FH
cells develop and function.
Key features of T
FH
cells are dictated by their dynamic interactions with cognate and bystander B cells and shaped by the tissue environment they traverse during distinct spatiotemporal stages of T cell-dependent B cell responses.
Chance escape from an inhibitory tissue milieu and chance encounter with a conducive environment underlies the development of T
FH
cells.
T
FH
cells contribute to the development of memory CD4
+
T cell populations, and progression through an intermediate T
FH
cell stage may even be the predominant pathway for the formation of central memory T cell populations.
A model of default T
FH
cell development with inherent spatiotemporal stochasticity is proposed.
This Review discusses our current understanding of the development and functions of follicular helper T (T
FH
) cells. The author explains how these cells do not fit with the classical instructional model of helper T cell differentiation and, instead, proposes a model of default T
FH
cell development with inherent spatiotemporal stochasticity.
T follicular helper (T
FH
) cells play a crucial part in the development of humoral immunity by controlling the formation of, and the cellular reactions that occur in, germinal centres. Within these organized lymphoid tissue microstructures, B cells proliferate and somatically mutate to produce long-lived, high-affinity plasma cells and memory B cells. T
FH
cells exhibit unique molecular, cellular and tissue-dynamic features that are integral to their development and function but that are not necessarily compatible with the classical paradigm of effector CD4
+
T cell differentiation. Here, I discuss recent advances in T
FH
cell biology and their implications for our understanding of T cell differentiation and memory in humoral immunity from spatiotemporal and functional perspectives.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Antigens
/ Biology
/ Cell Communication - immunology
/ Cell Differentiation - genetics
/ Cell Differentiation - immunology
/ Cells
/ Clonal Selection, Antigen-Mediated
/ Germinal Center - immunology
/ Germinal Center - metabolism
/ Growth
/ Humans
/ Immunity, Humoral - genetics
/ Immunity, Humoral - immunology
/ Immunological Synapses - immunology
/ Lymphocyte Activation - genetics
/ Lymphocyte Activation - immunology
/ T cells
/ T-Lymphocytes, Helper-Inducer - cytology
/ T-Lymphocytes, Helper-Inducer - immunology
/ T-Lymphocytes, Helper-Inducer - metabolism
/ Vaccines
