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.[1] 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[2] and IL-4.[3] 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.[4][5]

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,[6] although the exact mechanisms involved are still unknown.[7] 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.[8][9] 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.[10]

Role of CD40L

In germinal centers, antigen-experienced TFH cells rapidly upregulate the expression of CD40L, which binds with B cell surface protein CD40 in B cell-T cell zone vicinity.[11] The TFH cell CD40L and B cell CD40 crosstalk modulates the intracellular receptor and gene expression inside the B cell, including induction of AID (Activation-Induced Cytidine Deaminase).[12] AID (AICDA) expression causes B cell antibodies to class switch from IgM/IgD to other antibody isotypes and drives somatic hypermutation during clonal proliferation. The switched antibodies acquire better effector functions, and hypermutated antibody shows greater affinity for antigen. The exact mechanism of AID-mediated B cell maturation is not clear.

TFH and Cholera

Vibrio cholerae infected patients and healthy human volunteers administered with existing cholera vaccine are recently studied in Bangladeshi population by Dr. Firdausi Qadri and her group. They have shown that the Memory TFH response is cholera antigen specific and has correlation with further antibody production by B cells.[13]


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.[7]


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