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  • Review Article
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T follicular helper cells in space-time

Nature Reviews Immunology volume 16, pages 612–625 (2016)Cite this article

Subjects

Key Points

  • T follicular helper (TFH) 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.

  • TFH 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 TFH cells develop and function.

  • Key features of TFH 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 TFH cells.

  • TFH cells contribute to the development of memory CD4+ T cell populations, and progression through an intermediate TFH cell stage may even be the predominant pathway for the formation of central memory T cell populations.

  • A model of default TFH cell development with inherent spatiotemporal stochasticity is proposed.

Abstract

T follicular helper (TFH) 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. TFH 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 TFH cell biology and their implications for our understanding of T cell differentiation and memory in humoral immunity from spatiotemporal and functional perspectives.

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Figure 1: Three phases of a T cell-dependent B cell response.
Figure 2: Germinal centre T cell–B cell interactions and intercellular positive feedback.
Figure 3: The follicular niche for TFH cell conditioning.
Figure 4: Default TFH cell development with spatiotemporal stochasticity.

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Acknowledgements

This work was supported by a National Natural Science Foundation of China grant (81330070) and by National Natural Science Funds for Distinguished Young Scholar (81425011). The author apologizes to investigators whose contributions were not cited more extensively because of space limitations.

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  1. Department of Basic Biomedical Sciences, Laboratory of Dynamic Immunobiology, Institute for Immunology, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Medical Science Building A107, Tsinghua University, Beijing, 100084, China

    Hai Qi

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Qi, H. T follicular helper cells in space-time. Nat Rev Immunol 16, 612–625 (2016). https://doi.org/10.1038/nri.2016.94

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