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Sci Transl Med. 2014 Aug 6;6(248):248ra106. doi: 10.1126/scitranslmed.3008930.

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

Author information

1
Department of Neurology, UCSF, San Francisco, CA 94148 USA.
2
Rinat-Pfizer Inc., 230 East Grand Avenue, South San Francisco, CA 94080, USA.
#
Contributed equally

Abstract

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, CD27(hi)CD38(hi) plasma cells/plasmablasts, or CD27(-)IgD(-) 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.

PMID:
25100740
PMCID:
PMC4176763
DOI:
10.1126/scitranslmed.3008930
[Indexed for MEDLINE]
Free PMC Article

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