Multiple sclerosis (MS) is a neuroinflammatory disease driven by B- and T-cells. The role of follicular regulatory T cells (Tfr) in MS remains ill-defined. Here, we found the clinical activity of MS patients to follow the frequency of circulating Tfr, suggesting that Tfr promote clinical relapse. Furthermore, Tfr-deficient mice underwent less severe experimental autoimmune encephalomyelitis than wild-type mice, which correlated with a decrease in Bcells infiltrating the central nervous system (CNS). Mechanistically, Tfr deficiency led to the trapping of B-cells in germinal centers of second lymphoid organs through B-cell overexpression of the sphingosine-1-phosphate receptor 2 (S1PR2). Tfr conversely promoted encephalomyelitis by downregulating S1PR2, which allowed B-cells to egress from germinal centers and migrate to the CNS, where they promoted cytokine production by encephalitogenic T-cells. Together, these findings demonstrate that Tfr contribute to autoimmune encephalomyelitis, and that Tfr frequency in blood reflects MS activity. Accordingly, the present invention relates to a method for predicting active disease in a subject suffering from multiple sclerosis, said method comprising the step of determining the frequency of Follicular Regulatory T (Tfr) cells in a population of cells in a sample obtained from the subject