The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo

ICOS is a new member of the CD28 family of costimulatory molecules that is expressed on activated T cells. Its ligand B7RP-1 is constitutively expressed on B cells. Although the blockade of ICOS/B7RP-1 interaction inhibits T cell-dependent Ab production and germinal center formation, the mechanism remains unclear. We examined the contribution of ICOS/B7RP-1 to the generation of CXCR5(+) follicular B helper T (T-FH) cells in vivo, which preferentially migrate to the B cell zone where they provide cognate help to B cells. In the spleen, anti-B7RP-1 mAb-treated or ICOS-deficient mice showed substantially impaired development of CXCR5(+) T-FH cells and peanut agglutinin(+) germinal center B cells in response to primary or secondary immunization with SRBC. Expression of CXCR5 on CD4(+) T cells was associated with ICOS expression. Adoptive transfer experiments showed that the development of CXCR5(+) T-FH cells was enhanced by interaction with B cells, which was abrogated by anti-B7RP-1 mAb treatment. The development of CXCR5(+) T-FH cells in the lymph nodes was also inhibited by the anti-B7RP-1 mAb treatment. These results indicated that the ICOS/B7RP-1 interaction plays an essential role in the development of CXCR5(+) T-FH cells in vivo.