Follicular helper T cell-mediated mucosal barrier maintenance

• The intestinal microbiome establishes and is maintained by germinal centers (GCs).
• High-affinity IgA maintains commensals in the gut under steady-state.
• Follicular helper T cells (Tfh) are essential for mucosa-associated GCs.
• Tfh cells exhibit phenotypic plasticity with other CD4 T cells in the gut.

The basic functions of the immune system are protection from pathogens and maintenance of tolerance to self. The maintenance of commensal microbiota at mucosal surfaces adds a layer of complexity to these basic functions. Recent reports suggest follicular helper T cells (Tfh), a CD4+ T cell subset specialized to provide help to B cells undergoing isotype switching and affinity maturation in germinal centers (GC), interact with the microbiota and are essential to maintenance of mucosal barriers. Complicating the issue is ongoing controversy in the field regarding origin of the Tfh subset and its distinction from other effector CD4 T cell phenotypes (Th1/Th17/Treg). This review focuses on the differentiation, phenotypic plasticity, and function of CD4 T cells, with an emphasis on commensal-specific GC responses in the gut.