Expression of Foxp3 by T follicular helper cells in end-stage germinal centers

Abstract

Germinal centers (GCs) are the site of immunoglobulin somatic hypermutation and affinity maturation, processes essential to an effective antibody response. The formation of GCs has been studied in detail, but less is known about what leads to their regression and eventual termination, factors that ultimately limit the extent to which antibodies mature within a single reaction. We show that contraction of immunization-induced GCs is immediately preceded by an acute surge in GC-resident Foxp3⁺ T cells, attributed at least partly to up-regulation of the transcription factor Foxp3 by T follicular helper (T_FH) cells. Ectopic expression of Foxp3 in T_FH cells is sufficient to decrease GC size, implicating the natural up-regulation of Foxp3 by T_FH cells as a potential regulator of GC lifetimes.