Follicular B Helper T cells

Follicular B helper T cells (also known as just Follicular helper T cells or TFH), are antigen-experienced CD4+ T cells found in the B cell follicles of secondary lymphoid organs such as lymph nodes, spleens and Peyer's patches, and are identified by their constitutive expression of the B cell follicle homing receptor CXCR5. TFH cells are found within B cell follicles and mediate antigen specific naïve or memory B cell activation, which triggers germinal center formation, probably through the expression of CD40L and the secretion of IL-21 and IL-4. It is possible that TFH cells might arise as branches in the Th1 and Th2 differentiation pathways but their precise lineage relationship to the other effector CD4+ T cell subsets is still uncertain. Recent studies have however shown that TFH have distinct gene expression profiles, supporting the theory that TFH are a subset of CD4+ T cells distinct from Th-1, Th-2, Th-17 or Tregs.

Role of ICOS
The Inducible T-cell co-stimulator (CD278 or ICOS) has proven to provide a particularly critical signal for TFH cells since mice deficient in ICOS are unable to develop any TFH, although the exact mechanisms involved are as of yet unknown. However, it was shown that ICOS induces the secretion of IL-21 by activated CD4+ T cells and that IL-21 plays a crucial role in the development of TFH. Also Bcl-6 is a transcription factor identified in TFH cells, but it may have roles that extend beyond this subset, because it has been implicated in memory CD8+ T cell development. .

Autoimmunity
Finally, it has been shown that dysregulated TFH cells can cause systemic autoimmunity and auto-antibody production or contribute to T cell–mediated organ-specific autoimmunity.