Follicular helper T cells (also known as T follicular helper cells and abbreviated as TFH), are antigen-experienced CD4+ T cells found in the periphery within B cell follicles of secondary lymphoid organs such as lymph nodes, spleen and Peyer's patches, and are identified by their constitutive expression of the B cell follicle homing receptor CXCR5.[1] Upon cellular interaction and cross-signaling with their cognate follicular (Fo B) B cells, TFH cells trigger the formation and maintenance of germinal centers through the expression of CD40 ligand (CD40L) and the secretion of IL-21[2] and IL-4.[3] TFH cells also migrate from T cell zones into these seeded germinal centers, predominantly composed of rapidly dividing B cells mutating their Ig genes. Within germinal centers, TFH cells play a critical role in mediating the selection and survival of B cells that go on to differentiate either into long-lived plasma cells capable of producing high affinity antibodies against foreign antigen, or germinal center-dependent memory B cells capable of quick immune re-activation in the future if ever the same antigen is re-encountered.[4] TFH cells are also thought to facilitate negative selection of potentially autoimmune-causing mutated B cells in the germinal center. However, the biomechanisms by which TFH cells mediate germinal center tolerance are yet to be fully understood.
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. 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.[5][6]
The function of TFH cells. A subset of naive T cells in the T cell zone are activated by antigen and migrate to the follicles where they differentiate into TFH cells that interact with and instruct Follicular B (Fo B) cells to undergo isotype switching, somatic hypermutation, and rapid cellular division to seed germinal centers (GC). Within these germinal centers, TFH cells continue to provide help to GC B cells to facilitate their production of high affinity antibody producing plasma cells (PC) and long-lived memory (Mem) B cells.
^Fazilleau; Mark, L; McHeyzer-Williams, LJ; McHeyzer-Williams, MG; et al. (March 2009). "Follicular helper T cells: lineage and location". Immunity. 30 (3): 324–35. doi:10.1016/j.immuni.2009.03.003. PMC 2731675. PMID 19303387.
^Seo; Youn, J; Kim, PH; et al. (May 2009). "IL-21 ensures TGF-beta 1-induced IgA isotype expression in mouse Peyer's patches". J Leukoc Biol. 85 (5): 744–50. doi:10.1189/jlb.0708450. PMID 19168593. S2CID 22358429.
^Zaretsky; Taylor, JJ; King, IL; Marshall, FA; Mohrs, M; Pearce, EJ; et al. (May 2009). "T follicular helper cells differentiate from Th2 cells in response to helminth antigens". J Exp Med. 206 (5): 991–9. doi:10.1084/jem.20090303. PMC 2715032. PMID 19380637.
^Kurosaki; Kometani, K; Ise, W (March 2015). "Memory B cells". Nat Rev Immunol. 15 (3): 149–59. doi:10.1038/nri3802. PMID 25677494. S2CID 20825732.
^Chtanova; Tangye, SG; Newton, R; Frank, N; Hodge, MR; Rolph, MS; MacKay, CR; et al. (July 2004). "T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells". J Immunol. 173 (1): 68–78. doi:10.4049/jimmunol.173.1.68. PMID 15210760.
^Nurieva RI, Chung Y, Hwang D, Yang XO, Kang HS, Ma L, Wang YH, Watowich SS, et al. (2008). "Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages". Immunity. 29 (1): 138–49. doi:10.1016/j.immuni.2008.05.009. PMC 2556461. PMID 18599325.
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