Clonal relationships of CSF B cells in treatment-naive multiple sclerosis patients

Erica L. Eggers, Brady A. Michel, Hao Wu, Sheng Zhi Wang, Carolyn J. Bevan, Aya Abounasr, Natalie S. Pierson, Antje Bischof, Max Kazer, Elizabeth Leitner, Ariele L. Greenfield, Stanislas Demuth, Michael R. Wilson, Roland G. Henry, Bruce Ac Cree, Stephen L. Hauser, H. Christian von Büdingen

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

A role of B cells in multiple sclerosis (MS) is well established, but there is limited understanding of their involvement during active disease. Here, we examined cerebrospinal fluid (CSF) and peripheral blood (PB) B cells in treatment-naive patients with MS or high-risk clinically isolated syndrome. Using flow cytometry, we found increased CSF lymphocytes with a disproportionate increase of B cells compared with T cells in patients with gadolinium-enhancing (Gd+) lesions on brain MRI. Ig gene heavy chain variable region (Ig-VH) repertoire sequencing of CSF and PB B cells revealed clonal relationships between intrathecal and peripheral B cell populations, which could be consistent with migration of B cells to and activation in the CNS in active MS. In addition, we found evidence for bystander immigration of B cells from the periphery, which could be supported by a CXCL13 gradient between CSF and blood. Understanding what triggers B cells to migrate and home to the CNS may ultimately aid in the rational selection of therapeutic strategies to limit progression in MS.

Original languageEnglish (US)
JournalJCI Insight
Volume2
Issue number22
DOIs
StatePublished - Nov 16 2017

Keywords

  • Autoimmunity
  • B cells
  • Multiple sclerosis
  • Neuroscience

ASJC Scopus subject areas

  • Medicine(all)

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