Sphingosine 1-phosphate receptor agonist FTY720-phosphate causes marginal zone B cell displacement

Abstract: FTY720 is an immunosuppressive agent that modulates lymphocyte trafficking. It is phosphorylated in vivo to FTY720-phosphate (FTY-P) and binds to a family of G protein-coupled receptors recognizing sphingosine 1-phosphate (S1P) as the natural ligand. It has previously been reported that FTY-P blocks egress of lymphocytes from the thymus and lymph nodes, resulting in peripheral blood lymphopenia. We now report that FTY-P also causes displacement of marginal zone (MZ) B cells to the splenic follicles, an effect that is similar to that observed after in vivo administration of lipopolysaccharide. This effect is specific to B cells in the MZ, as treatment with FTY-P does not cause redistribution of the resident macrophage population. A small but statistically significant de-crease in the expression of 1 integrin on MZ B cells was observed with FTY-P treatment. The re-distribution of MZ B cells from the MZ sinuses does not abolish the ability of these cells to respond to the T-independent antigen, trinitrophenol-Ficoll. It has been proposed that the displacement of MZ B cells to the follicles is an indication of cell activa-tion. Consistent with this, FTY-P caused an in-crease in percentage of MZ B cells expressing ac-tivation markers CD9, CD1d, and CD24. These results suggest that S1P receptors on MZ B cells are responsible for their mobilization to follicles. J