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Annu Rev Immunol. 2016 May 20;34:335-68. doi: 10.1146/annurev-immunol-041015-055605. Epub 2016 Feb 22.

Follicular Helper T Cells.

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Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia; email:
Lymphocyte Signalling and Development Institute Strategic Programme, Babraham Institute, Cambridge CB22 3AT, United Kingdom; email:
Laboratory for Molecular Immunomodulation, Department of Biochemistry and Molecular Biology, and Center for Inflammatory Diseases, Monash University, Melbourne, Victoria 3800, Australia; email:
School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom.


Although T cell help for B cells was described several decades ago, it was the identification of CXCR5 expression by B follicular helper T (Tfh) cells and the subsequent discovery of their dependence on BCL6 that led to the recognition of Tfh cells as an independent helper subset and accelerated the pace of discovery. More than 20 transcription factors, together with RNA-binding proteins and microRNAs, control the expression of chemotactic receptors and molecules important for the function and homeostasis of Tfh cells. Tfh cells prime B cells to initiate extrafollicular and germinal center antibody responses and are crucial for affinity maturation and maintenance of humoral memory. In addition to the roles that Tfh cells have in antimicrobial defense, in cancer, and as HIV reservoirs, regulation of these cells is critical to prevent autoimmunity. The realization that follicular T cells are heterogeneous, comprising helper and regulatory subsets, has raised questions regarding a possible division of labor in germinal center B cell selection and elimination.


B follicular helper T (Tfh) cell; antibody responses; germinal center

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