Short-lived plasma blasts are the main B cell effector subset during the course of multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder of the central nervous system (CNS) with an unknown etiology. Although intrathecal IgG synthesis is a key feature of the disease, little is still known about the B cell response in the CNS of MS patients. Here, we analyzed the phenotype and kinetics of different B cell subsets in patients with MS, infectious (IND) and non-inflammatory neurological diseases (NIND). B cells were detected in the CSF of MS and IND patients, but were largely absent in NIND patients. In the CSF the majority of B cells had a phenotype of memory B cells and short-lived plasma blast (PB), plasma cells were absent from the compartment. The proportion of PB was highest in MS patients and patients with acute CNS infection. While PB rapidly disappeared from the CSF after resolution of infection in IND patients, these cells were present at high numbers throughout the disease course in MS patients. CSF PB numbers in MS patients strongly correlated with intrathecal IgG synthesis and inflammatory parenchymal disease activity as disclosed by MRI. This study identifies short-lived plasma blasts as the main effector B cell population involved in ongoing active inflammation in MS patients.