Abundance of follicular helper T cells in Peyer's patches is modulated by CD155

The secondary humoral immune response is characterized by plasma B cells secreting isotype-switched and affinity-matured antibodies. The efficient generation of plasma B cells in the GC depends on the presence of follicular helper T (T-FH) cells, a cell type thought to arise from naive CD4-positive T cells by a hitherto unresolved differentiation pathway. Mice deficient for CD155, an adhesion receptor of the immunoglobulin superfamily, are impaired to mount a secondary humoral immune response upon oral administration of antigen, while the primary IgM response is unaffected. Here, we show that mice lacking CD155 harbor significantly reduced numbers of T-FH cells in their Peyer's patches. This was paralleled by a decreased frequency of T-FH cells in the GC. Moreover, the CD155 ligand CD226, which is involved in T-cell activation, is down-regulated during T-FH cell differentiation, resulting in a complete absence of CD226 on those T-FH cells residing in the GC. Concurrently, the expression of TIGIT/WUCAM, a newly discovered CD155 ligand, is induced in T-FH cells. Thus, these cells replace an activating by a putative inhibitory CD155-binding partner during their differentiation.