Follicular helper T cells, or Tfh cells, have a crucial role in immune defense. Without Tfh cells, B cells cannot form germinal center, or GC, responses during which high-affinity antibodies are generated.
When naïve CD4-positive CD4+ T cells receive news of an infection elsewhere in the body, they become activated with additional cell-surface markers, and they differentiate in two directions, becoming either PD-1+CXCR5– or PD-1+CXCR5+ T cells. PD-1 and CXCR5 are two different cell-surface markers, and the plus and minus signs tell whether they are present or absent.
The PD-1+CXCR5+CD4+ T cells have the capacity to differentiate, move into B-cell follicles and mature into GC-Tfh cells. These GC-Tfh cells are essential for the formation of germinal centers, the place where B cells generate high-affinity antibodies.
But there was a mystery about these PD-1+CXCR5+CD4+ T cells. While some PD-1+CXCR5+CD4+ cells enter the follicle, others do not. Now Hui Hu, Ph.D., and colleagues at the University of Alabama at Birmingham have identified a cell-surface marker that indicates which T cells will go into the follicles and which ones will stay out. A sustained appearance of the cell-surface protein, Tigit, identifies the Tigit-positive PD-1+CXCR5+CD4+ T cells, or pre-Tfh, that will become GC-Tfh cells, they report in a study published in Nature Communications.
“Which of the PD-1+CXCR5+CD4+ T cells will differentiate into PD-1hiCXCR5hi GC-Tfh cells while the others have