Additionally, it has been shown that ICOS induces the secretion of IL-21 cytokine by activated CD4 + T cells and that IL-21 plays a crucial role in the development of T FH cells and germinal centers. The inducible T-cell co-stimulator ( CD278 or ICOS) is proven to provide a particularly critical signal for T FH cells since experimental mice deficient in ICOS are unable to develop any T FH.
Within these germinal centers, T FH 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. Ī subset of naive T cells in the T cell zone are activated by antigen and migrate to the follicles where they differentiate into T FH 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). Studies have however shown that T FH have distinct gene expression profiles, supporting the theory that T FH are a subset of CD4 + T cells distinct from Th-1, Th-2, Th-17 or Tregs. It is possible that T FH 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. However, the biomechanisms by which T FH cells mediate germinal center tolerance are yet to be fully understood. T FH cells are also thought to facilitate negative selection of potentially autoimmune-causing mutated B cells in the germinal center. Within germinal centers, T FH 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. T FH cells also migrate from T cell zones into these seeded germinal centers, predominantly composed of rapidly dividing B cells mutating their Ig genes. Upon cellular interaction and cross-signaling with their cognate follicular (Fo B) B cells, T FH cells trigger the formation and maintenance of germinal centers through the expression of CD40 ligand (CD40L) and the secretion of IL-21 and IL-4. Follicular helper T cells (also known as follicular B helper T cells and abbreviated as T FH), 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.
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