T follicular helper cell differentiation

Definition

Target type: biologicalprocess

The process in which a relatively unspecialized T cell acquires specialized features of a mature T follicular helper cell. [GOC:dph, PMID:21572431]

T follicular helper (Tfh) cell differentiation is a complex process that involves a series of molecular and cellular events leading to the development of specialized CD4+ T cells that provide help to B cells in germinal centers to produce high-affinity antibodies. This process is initiated when naive CD4+ T cells encounter antigen presented by antigen-presenting cells (APCs), such as dendritic cells, in the context of costimulatory signals and cytokines. Upon antigen recognition, naive CD4+ T cells become activated and differentiate into various effector T cell subsets, including Tfh cells.

The differentiation of Tfh cells is characterized by the expression of a specific set of transcription factors and chemokine receptors, including Bcl6, CXCR5, and ICOS. Bcl6 is a key transcription factor that promotes Tfh cell differentiation by repressing the expression of genes associated with other T cell lineages, such as Th1, Th2, and Th17 cells. CXCR5 is a chemokine receptor that directs Tfh cells to migrate to the B cell zone of secondary lymphoid organs, such as lymph nodes and spleen. ICOS is a costimulatory molecule that enhances Tfh cell activation and function.

The differentiation of Tfh cells is also influenced by the cytokine environment. Interleukin-21 (IL-21) is a key cytokine that promotes Tfh cell differentiation and function. IL-21 is produced by both Tfh cells and other immune cells, such as B cells and dendritic cells. It acts in an autocrine and paracrine manner to enhance Tfh cell development and function.

Once Tfh cells migrate to the germinal center, they interact with B cells that have also encountered antigen. Tfh cells provide help to B cells through the secretion of cytokines, such as IL-21 and IL-4, and by expressing the surface molecule CD40L, which interacts with CD40 on B cells. These signals stimulate B cell proliferation, class-switch recombination, and somatic hypermutation, leading to the production of high-affinity antibodies that are critical for adaptive immunity.

The development and function of Tfh cells are tightly regulated by various factors, including the nature of the antigen, the strength of the TCR signal, and the presence of costimulatory molecules and cytokines. The dysregulation of Tfh cell differentiation or function has been linked to various autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, as well as to chronic infections and cancer. Therefore, understanding the molecular and cellular mechanisms underlying Tfh cell differentiation is essential for developing novel therapeutic strategies for these diseases.'
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Proteins (1)

Compounds (2)