Research ArticleMultiple Sclerosis

Immunoglobulin class-switched B cells form an active immune axis between CNS and periphery in multiple sclerosis

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Science Translational Medicine  06 Aug 2014:
Vol. 6, Issue 248, pp. 248ra106
DOI: 10.1126/scitranslmed.3008930

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In multiple sclerosis (MS), lymphocyte—in particular B cell—transit between the central nervous system (CNS) and periphery may contribute to the maintenance of active disease. Clonally related B cells exist in the cerebrospinal fluid (CSF) and peripheral blood (PB) of MS patients; however, it remains unclear which subpopulations of the highly diverse peripheral B cell compartment share antigen specificity with intrathecal B cell repertoires and whether their antigen stimulation occurs on both sides of the blood-brain barrier. To address these questions, we combined flow cytometric sorting of PB B cell subsets with deep immune repertoire sequencing of CSF and PB B cells. Immunoglobulin (IgM and IgG) heavy chain variable (VH) region repertoires of five PB B cell subsets from MS patients were compared with their CSF Ig-VH transcriptomes. In six of eight patients, we identified peripheral CD27+IgD memory B cells, CD27hiCD38hi plasma cells/plasmablasts, or CD27IgD B cells that had an immune connection to the CNS compartment. Pinpointing Ig class-switched B cells as key component of the immune axis thought to contribute to ongoing MS disease activity strengthens the rationale of current B cell–targeting therapeutic strategies and may lead to more targeted approaches.

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