T follicular helper cell differentiation, function, and roles in disease

By Shane Crotty. 2014

1,696 citations recorded by the source corpus.

Summary Follicular helper T (Tfh) cells are specialized providers of T cell help to B cells, and are essential for germinal center formation, affinity maturation, and the development of most high affinity antibodies and memory B cells. Tfh cell differentiation is a multi-stage, multi-factorial process involving B cell lymphoma 6 (Bcl6) and other transcription factors. This article reviews understanding of Tfh cell biology, including their differentiation, migration, transcriptional regulation, and B cell help functions. Tfh cells are critical components of many protective immune responses against pathogens. As such, there is strong interest in harnessing Tfh cells to improve vaccination strategies. Tfh cells also have roles in a range of other diseases, particularly autoimmune diseases. Overall, there have been dramatic advances in this young field, but there is much to be learned about Tfh cell biology in the interest of applying that knowledge to biomedical needs.

Subfields: Genetics, Immunology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. David Baker
2. Lauren P. Carter
3. D. Veesler

In Immunology

1. F. Sallusto
2. A. Lanzavecchia
3. Erika L. Pearce
4. Shane Crotty
5. Eran Elinav
6. Rafi Ahmed
7. Bali Pulendran
8. V. Schirrmacher

Citations in the corpus

• Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus (2019, background): “Cellular Responses to I53-50, DS-Cav1, and DS-Cav1I53-50 To determine whether T follicular helper (Tfh) cells, essential regulators of B cell maturation in germinal centers (GCs) (Crotty, 2014), play a role in the enhanced immunogenicity of DSCav1-I53-50, we compared the total numbers of Tfh and GC ”
• Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens (2017, background): “GCs are the anatomic site in which activated B cells undergo the process of SHM and T follicular helper (Tfh) cell-driven selection in response to immunization or infection, in the Darwinian process of affinity maturation (Crotty, 2014; Eisen, 2014).”
• T follicular helper cell biology: A decade of discovery and diseases (2019, background): “Memory Tfh cells appear to be derived from GC-Tfh cells or mTfh cells (Crotty, 2014; Tubo et al., 2016) and constitute a major fraction of human memory CD4+ T cells.”
• Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19 (2020, positive): “The differentiation of CD4+Bcl-6 CXCR5+ pre-germinal center TFH cells into CD4 +Bcl-6+CXCR5+ GC-TFH cells likely occurs extra-follicularly at the T-B interface (Kerfoot et al., 2011; Kitano et al., 2011; Crotty, 2014; Vinuesa et al., 2016).”
• GERMINAL CENTER B CELL DYNAMICS (2016, neutral): “There has been a dramatic increase in our knowledge of Tfh cell biology in recent years, and there are excellent reviews on the subject (Crotty, 2014; Vinuesa et al., 2016).”
• Interaction between microbiota and immunity in health and disease (2020, background): “Follicular helper T (Tfh) cells are specialized to assist B cells, and are crucial for germinal center formation, affinity maturation, and generation of high-affinity antibody responses and memory B cells.(116) Tfh cells are implicated in maintenance of microbiota homeostasis as highlighted by studi”
• Unraveling the Complex Interplay Between T Cell Metabolism and Function (2018, background): “T follicular helper (Tfh) cells, unlike other CD4+ Te cell subsets, persist in the lymph node after activation, where they are essential for supporting B cell survival and antibody production (115).”