Brain Advance Access originally published online on March 30, 2005
Brain 2005 128(7):1667-1676; doi:10.1093/brain/awh486
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Short-lived plasma blasts are the main B cell effector subset during the course of multiple sclerosis
1 Department of Neurology, Heinrich Heine-University, Duesseldorf and 2 Department of Neurology, Philipps-University, Marburg, Germany
Correspondence to: Bernhard Hemmer, M.D., Neuroimmunology Group, Department of Neurology, Heinrich Heine-University, Moorenstr. 5, 40225 Duesseldorf, Germany E-mail: bernhard.hemmer{at}uni-duesseldorf.de
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.
Key Words: Plasma blasts; B cells; multiple sclerosis; cerebrospinal fluid
Abbreviations: EAE = experimental autoimmune encephalomyelitis; FCS = fetal calf serum; Gd = gadolinium; Ig = immunoglobulin; IgIF = intrathecally produced fraction of Ig; IND = infectious CNS disease; mAb = monoclonal antibody; NB = neuroborreliosis; NIND = non-inflammatory neurological disease; PB = plasma blasts; PBS = phosphate-buffered saline; PC = plasma cells; VM = viral meningitis
Received January 3, 2005. Revised February 15, 2005. Accepted February 23, 2005.
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