T Follicular Helper Cell Pathway
T follicular helper (Tfh) cells are a specialized subset of T helper cells that provide help to B cells and are essential for affinity maturation and antibody production. Expression of CXCR5 on the cell surface drives the movement of an early Tfh cell to the edge of the T cell zone and B cell follicle. Here, additional stimulation through ICOS and ICOSL binding is required for further development into a fully mature Tfh cell. The presence of IL-21 and the absence of TGF-β drive this process. Mature Tfh cells can be identified by their expression of STAT3 and Bcl-6 transcription factors. Tfh cells drive germinal center formation through secretion of important cytokines including IL-21. Once in the follicle, Tfh cells rapidly upregulate the expression of cell surface markers like CD40L which bind to their respective ligands on the B cell and promote class switching. Dysfunction of Tfh cells is associated with a number of autoimmune diseases including lupus and rheumatoid arthritis. Tfh cells also play a role in HIV infection and can contribute to viral infection and serve as an HIV reservoir.
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