Our finding that CSF B cells are correlated with other paraclinical markers of acute brain inflammation such as high numbers of MRI T2 lesions, the presence of Gd-enhancing MRI lesions, total number of CSF cells, intrathecal IgM and IgG synthesis and intrathecal MMP-9 and CxCL-13 production indicate a direct involvement of B cells in acute brain inflammation. Here, CD40LG is linked to brain inflammatory disease.