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

Abstract

Multiple sclerosis is a chronic inflammatory and demyelinating disorder of the CNS with an unknown aetiology. Although intrathecal immunoglobulin G (IgG) synthesis is a key feature of the disease, little is still known about the B cell response in the CNS of multiple sclerosis patients. We analysed the phenotype and kinetics of different B cell subsets in patients with multiple sclerosis, infectious disease (IND) and non-inflammatory neurological disease (NIND). B cells were detected in the CSF of multiple sclerosis 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 blasts (PB); plasma cells were absent from the compartment. The proportion of PB was highest in multiple sclerosis patients and patients with acute CNS infection. While PB disappeared rapidly from the CSF after resolution of infection in IND patients, these cells were present at high numbers throughout the disease course in multiple sclerosis patients. CSF PB numbers in multiple sclerosis 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 multiple sclerosis patients.

Selective intrathecal enrichment of G1m1‐positive B cells in multiple sclerosis

“…Further characterization of the IgG1 ASCs in the CSF of MS patients showed that these cells express CD38, CD138, and HLA‐DR, together with dim levels of CD19 and high levels of CD27. This is in line with the results of a previous study characterizing intrathecal B cells,15 but contrasts another study that demonstrated increased numbers of CD19 – CD138 + plasma cells 16. Importantly, we show for the first time that the intrathecal IgG1 ASCs express high levels of Ki‐67, suggesting that the cells are newly derived and proliferate intrathecally.…”

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

“…Increased numbers of T cells and B cells are found in the CSF of patients with CNS infections or multiple sclerosis [3,16].…”

Genetic and Molecular Approaches to the Immunopathogenesis of Multiple Sclerosis: An Update

“…An important question is whether B cell stimulation only takes place outside the CNS, or if it also occurs intrathecally. The latter possibility is now supported by converging evidence: i) all B cell subsets, including centroblasts typical of secondary lymphoid organs, are present in the CSF of MS patients [236], ii) Short-lived plasma blasts are common in the CSF and their number correlates with intrathecal IgG synthesis, whereas long-lived plasma cells which are independent of antigen stimulation are very rare [237], iii) sequence analysis of transcribed V genes in single sorted CSF cells has identified the same clonal populations in plasma blasts and plasma cells, suggesting ongoing development of antibody secreting cells [238], and iv) ectopic germinal centers are present in the meninges of some patients with secondary progressive MS [239,240].…”