Tfhceller

T follicular helper cells (Tfh cells) are a specialized subset of CD4+ T helper cells that coordinate B cell responses within germinal centers of secondary lymphoid organs. They are characterized by expression of the chemokine receptor CXCR5, which directs them to B cell follicles, and high levels of PD-1 and ICOS. The transcription factor BCL6 acts as the master regulator of Tfh differentiation. Tfh cells secrete cytokines, most notably interleukin-21 (IL-21), with IL-4 also contributing to B cell help.

Development of Tfh cells begins after antigen encounter, with dendritic cells providing initial signals that favor differentiation. Cytokines such as IL-6 and IL-21 promote Tfh formation and BCL6 expression, while IL-2 inhibits this pathway through STAT5 signaling. ICOS-ICOSL interactions are important for Tfh maturation and entry into germinal centers. Tfh cells can be further categorized into subsets (Tfh1, Tfh2, Tfh17) based on the cytokine environment they experience, which influences their helper profile for B cells.

Functionally, Tfh cells provide essential help to B cells in germinal centers through CD40L–CD40 interactions and cytokines, particularly IL-21. This assistance promotes somatic hypermutation, affinity maturation, and class-switch recombination, leading to the production of high-affinity antibodies and the generation of memory B cells and long-lived plasma cells. Circulating Tfh cells (cTfh) are detectable in peripheral blood and, while not identical to germinal center Tfh cells, can reflect GC activity in some contexts.

Clinical relevance includes the influence of Tfh cell frequency and function on vaccine-induced antibody responses and their involvement in autoimmune diseases such as systemic lupus erythematosus when dysregulated. They are also affected in chronic infections such as HIV, and their activity is balanced by follicular regulatory T cells.