Cytokine-Skewed Tfh Cells: Functional Consequences For B Cell Help

CD4+ follicular helper T (Tfh) cells play a vital role in providing help for B cells undergoing selection and differentiation into activated antibody-secreting cells in mammalian germinal centers (GCs). Increasing evidence suggests that Tfh cells are a heterogeneous population that generates cytokine-skewed immune responses-a reflection of the microenvironment during differentiation. This has important ramifications for Tfh-mediated B cell help. Because Tfh subsets can have opposing effects on GC B cell responses, we discuss current findings regarding the differentiation and functions of cytokine-skewed Tfh cells in modulating GC B cell differentiation. Antibodies are important weapons against infectious diseases but can also be pathogenic mediators in some autoimmune conditions. Since cytokine-skewed Tfh cells can influence the magnitude and quality of the humoral response, we address the roles of cytokine-skewed Tfh cells in disease.Tfh cells are key players in the mammalian humoral immune response Plasma cells that secrete class-switched (see Glossary) high-affinity antibodies and long-lived memory B cells are the main cellular components conferring efficacious and long-lasting humoral responses against invading pathogens [1]. The ability of B cells to undergo selection and differentiation into long-lived plasma cells and memory B cells is dependent on signals from T follicular helper (Tfh) cells within GCs [2,3] (Figure 1). Tfh cells are a distinct T cell subset that can be distinguished from other CD4+ T cell subsets by their surface expression of C-X-C chemokine receptor 5 (CXCR5) [4,5], programmed cell death protein 1 (PD-1), and inducible T cell