Clonal relationships of CSF B cells in treatment-naïve multiple sclerosis patients. Homo sapiens

A role of B cells in multiple sclerosis (MS) is well established but there is limited understanding about their involvement during active disease. Here, we examined cerebrospinal fluid (CSF) and peripheral blood (PB) B cells in treatment-naïve patients with MS or high-risk clinically isolated syndrome (CIS). Using flow cytometry, we found increased CSF lymphocytes with a disproportionate increase of B cells compared to T cells in patients with gadolinium-enhancing (Gd+) lesions on brain MRI. Immunoglobulin gene heavy chain variable region (Ig-VH) repertoire sequencing of CSF and PB B cells revealed clonal relationships between intrathecal and peripheral B cell populations supporting migration of B cells to and activation in the CNS in active MS. CD27hi plasmablasts/plasma in CSF cells appear to derive from CNS or peripheral progenitors; presence of naïve B cells expressing identical Ig-VH in PB and CSF suggests by-stander immigration of B cells from the periphery which is supported by a CXCL13 gradient between CSF and blood. Understanding what triggers B cells to migrate and home to the CNS may ultimately aid in the rational selection of therapeutic strategies to limit progression in MS.