Follicular B helper T cells

Follicular helper T cells (also known as T follicular helper 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.^[1] 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^[2] and IL-4.^[3] 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. 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.^[4] T_FH cells are also thought to facilitate negative selection of potentially autoimmune-causing mutated B cells in the germinal center. However, the biomechanisms by which T_FH cells mediate germinal center tolerance are yet to be fully understood.

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. 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.^[5][6]