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T Follicular Helper Cells Express a Distinctive Transcriptional Profile, Reflecting Their Role as Non-Th1/Th2 Effector Cells That Provide Help for B Cells

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Chtanova, Tatyana, Tangye, Stuart G, Newton, Rebecca, Frank, Nita, Hodge, Martin R, Rolph, Michael S, Mackay, Charles R·2004·The Journal of Immunology

Abstract

Effector T cell responses have long been viewed in the context of the Th1/Th2 paradigm. Recently, a third major subset of nonpolarized effector T cells that provides help to B cells has been identified. These T cells, termed T follicular helper (TFH) cells, home to the B cell areas of secondary lymphoid tissue, through interactions mediated via the chemokine receptor CXCR5 and its ligand CXCL13. Affymetrix microarrays were used to identify transcription factors, cytokines, and cell surface molecules that underlie the differentiation pathways and functional properties of the TFH subset. The transcriptional profile of human CXCR5+ TFH cells was compared with that of Th1 and Th2 cells, which enabled the identification of numerous genes expressed preferentially by TFH cells, over the other effector subsets. Certain TFH genes were also expressed by B cells and thus appear to be particularly relevant for humoral immunity. Abs were used to confirm the expression of several factors. In particular, CD84 and CD200, the cytokine IL-21, and the transcription factor BCL6 were all strongly associated with TFH cells. Gene microarrays reveal a highly distinctive transcriptional profile for a third subset of effector T cells that differs markedly from Th1 and Th2 cells.

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Crossref · 10.4049/jimmunol.173.1.68

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  • Tfh cells are controlled by the transcription factor Bcl6.

    “Tfh cells are controlled by the transcription factor Bcl6 [197]”

    From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [197]

    The Discussion (page not supplied) reports that Tfh cells preferentially express BCL6 and suggests that BCL6 may act as a switch determining Th2 versus Tfh cell fate. It also says that a transcription factor directing Tfh differentiation had not yet been identified, so the categorical claim that BCL6 controls Tfh cells overstates the paper. (LLM, conf=0.87)

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Authors
Chtanova, T., Tangye, S. G., Newton, R., Frank, N., Hodge, M. R., Rolph, M. S., & Mackay, C. R.
Affiliations
  • The University of Sydney (AU)
  • Centenary Institute (AU)
  • Garvan Institute of Medical Research (AU)
  • Takeda Oncology (United States) (US)
Corresponding author
  • Chtanova, Tatyana
  • Newton, Rebecca
Venue
The Journal of Immunology
Published
2004-07-01
Volume
173
Issue
1
Pages
68-78
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W2113687173
Cited by
722
References
64
Citations by year
2026: 9 · 2025: 17 · 2024: 7 · 2023: 21 · 2022: 22 · 2021: 23 · 2020: 30 · 2019: 31 · 2018: 25 · 2017: 33 · 2016: 35 · 2015: 37 · 2014: 43 · 2013: 43 · 2012: 64
FWCI
8.87
Type
journal article
Language
en
Open access
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Medical Research Council
  • 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
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Keywords
T follicular helper cells, gene expression profiling, CXCR5, CXCL13, Th1/Th2 paradigm, B cell help, humoral immunity, CD84, CD200, IL-21, BCL6, T cell differentiation, secondary lymphoid organs
MeSH terms
Signaling Lymphocytic Activation Molecule Family, Interleukin-21, B-Lymphocytes, DNA-Binding Proteins, T-Lymphocytes, Helper-Inducer, Humans, Interleukins, Proto-Oncogene Proteins, Transcription Factors, Antigens, CD, Receptors, Cytokine, CD57 Antigens, Receptors, Chemokine, Gene Expression Profiling, Proto-Oncogene Proteins c-bcl-6, Receptors, CXCR5

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