Research ArticleMultiple Sclerosis

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

See allHide authors and affiliations

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

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution


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.

View Full Text

Stay Connected to Science Translational Medicine

Editor's Blog