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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibody Affinity / immunology
  • B-Lymphocytes / immunology*
  • Cell Aggregation
  • Central Nervous System / pathology*
  • Cerebrospinal Fluid / metabolism
  • Female
  • Flow Cytometry
  • Humans
  • Immune System / immunology*
  • Immunoglobulin Class Switching*
  • Immunoglobulin Variable Region / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology
  • Sequence Analysis, Protein
  • Somatic Hypermutation, Immunoglobulin / genetics
  • Young Adult


  • Immunoglobulin Variable Region

Associated data

  • SRA/SRP042205