Follicular helper T cells
Open accessAbstract
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.
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IL-6 promotes antibody production by directly acting on plasma cells and by indirectly promoting Bcl6-dependent follicular CD4+ T (Tfh) cell differentiation together with IL-21.
“Indeed, IL-6 promotes antibody production by directly acting on plasma cells and by indirectly promoting Bcl6-dependent follicular CD4(+) T (Tfh) cell differentiation together with IL-21 (Fig. 2) (143–146).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [146]
The section “Regulation of Human and Mouse T Follicular Helper Cells by Cytokines” says IL-6 and IL-21 contribute to Tfh differentiation in mice and that IL-6 induces an early wave of BCL6 expression. The passages do not say IL-6 directly acts on plasma cells to promote antibody production; the plasmablast effect described in “T Follicular Helper Effector Molecules” is attributed to IL-21. (LLM, conf=0.87)
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- Authors
- Vinuesa, C. G., Linterman, M. A., Yu, D., & MacLennan, I. C. M.
- Affiliations
- Australian National University (AU)
- Babraham Institute (GB)
- Monash University (AU)
- University of Birmingham (GB)
- Venue
- Annual Review of Immunology
- Publisher
- Annual Reviews
- Published
- 2016-05-20
- Volume
- 34
- Issue
- 1
- Pages
- 335-368
- ISSN
- 0732-0582 (ISSN-L)
- 1545-3278
- OpenAlex
- W2137446997
- Cited by
- 1,141
- References
- 9
- Citations by year
- 2026: 71 · 2025: 108 · 2024: 95 · 2023: 101 · 2022: 113 · 2021: 170 · 2020: 141 · 2019: 130 · 2018: 108 · 2017: 74 · 2016: 28 · 2015: 2
- FWCI
- 10.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Immunology (publishedVersion)
- PubMed (publishedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0407, BBS/E/B/000C0409)
- National Health and Medical Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Keywords
- T follicular helper cells, Tfh cell differentiation, CXCR5, BCL6, transcription factors, chemotactic receptors, germinal center, affinity maturation, B cell help, regulatory T cells, autoimmunity, HIV reservoir, tumor immunology, B cell selection
- MeSH terms
- Animals, B-Lymphocytes, Cell Differentiation, Gene Expression Regulation, T-Lymphocytes, Helper-Inducer, Humans, Immunologic Memory, Lymphocyte Activation, T-Lymphocyte Subsets, Germinal Center, MicroRNAs, Proto-Oncogene Proteins c-bcl-6, Receptors, CXCR5, Immunity, Humoral
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