Figure 1.

Early germinal center reaction and T follicular regulatory cell maturation process. Early Tfr (eTfr) derive from natural regulatory T cells (Tregs) after expression of CXCR5 and Bcl-6 and down regulation of FOXP3. After interaction with activated dendritic cells (DC) in the T cell zone, some eTfr lose expression of Bcl-6 and enter the circulation (blood Tfr-bTfr), while some migrate to the follicle (intermediate Tfr-iTfr), where they interact with the follicular B cells and start expressing PD-1 and ICOS. Eventually, they move to the germinal center (GC), becoming mature Tfr (mTfr), where they inhibit both the central T follicular helper cell (cTfh) and the GC B cells, leading to regulation of antibody production and B cell differentiation.