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

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.

journal_name

Sci Transl Med

authors

Palanichamy A,Apeltsin L,Kuo TC,Sirota M,Wang S,Pitts SJ,Sundar PD,Telman D,Zhao LZ,Derstine M,Abounasr A,Hauser SL,von Büdingen HC

doi

10.1126/scitranslmed.3008930

subject

Has Abstract

pub_date

2014-08-06 00:00:00

pages

248ra106

issue

248

eissn

1946-6234

issn

1946-6242

journal_volume

6

pub_type

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