Follicular T-helper cells: controlled localization and cellular interactions

Affinity-matured, isotype-switched antibodies afford humoral protection against microbial infections. Cells capable of producing such antibodies are derived from the germinal center (GC) formed during a T-dependent B-cell response. Follicular T-helper (T-FH) cells are a recently defined subset of CD4 T cells that are specialized in promoting the B-cell response and GC reaction. These cells exhibit a CXCR5(+)ICOS(hi)PD-1(hi) surface phenotype, express a high level of transcriptional repressor Bcl-6 and possess a unique ability to reside in the GC. Insights into how T-FH cells develop and function promise to refine our strategies toward more effective antibody-based vaccines and therapies for humoral autoimmunity. In this review, we summarize the current understanding of how T-FH-associated molecules regulate dynamic localization and B-cell-interacting properties of these cells, as both aspects are at the core of being T-FH cells.