Development and function of follicular helper T cells.

Most currently available vaccines rely on the induction of long-lasting protective humoral immune responses by memory B cells and plasma cells. Antibody responses against most antigens require interactions between antigen-specific B cells and CD4(+) T cells. Follicular helper T cells (TFH cells) are specialized subset of T cells that provide help to B cells and are essential for germinal center formation, affinity maturation, and the development of high-affinity antibodies. TFH-cell differentiation is a multistage process involving B-cell lymphoma 6 and other transcription factors, cytokines, and costimulation through inducible costimulator (ICOS) and several other molecules. This article reviews recent advances in our understanding of TFH cell biology, including their differentiation, transcriptional regulation, and function.