The contribution of B cells to the mechanisms of conversion to MS is shown not only by CSF B-cell associated biomarkers, but also by peripheral B cells. Kreutzfelder in 1992  showed a reduction of CD19+ peripheral blood in MS patients. This observation combined with the reduced percentage of CD19+ circulating cells in patients with a stable RR form of MS Bomgioanni  suggested that such a decrease is due to the sequestration of cells within the CNS. Lee-Chang  supported this theory by finding an up-regulation of α4 integrin on peripheral B cells that may enhance B-cell accumulation within the CSF at the time of CIS.