B Cell Exchange Across the Blood-brain Barrier in Multiple Sclerosis

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2012 Nov 20

PMID 23160197

Citations 113

Authors

H-Christian von Budingen

Tracy C Kuo

Marina Sirota

Christopher J van Belle

Leonard Apeltsin

Jacob Glanville

Bruce A Cree

Pierre-Antoine Gourraud

Amy Schwartzburg

Gabriella Huerta

Dilduz Telman

Purnima D Sundar

Tyler Casey

David R Cox

Stephen L Hauser

Affiliations

Soon will be listed here.

Abstract

In multiple sclerosis (MS) pathogenic B cells likely act on both sides of the blood-brain barrier (BBB). However, it is unclear whether antigen-experienced B cells are shared between the CNS and the peripheral blood (PB) compartments. We applied deep repertoire sequencing of IgG heavy chain variable region genes (IgG-VH) in paired cerebrospinal fluid and PB samples from patients with MS and other neurological diseases to identify related B cells that are common to both compartments. For the first time to our knowledge, we found that a restricted pool of clonally related B cells participated in robust bidirectional exchange across the BBB. Some clusters of related IgG-VH appeared to have undergone active diversification primarily in the CNS, while others have undergone active diversification in the periphery or in both compartments in parallel. B cells are strong candidates for autoimmune effector cells in MS, and these findings suggest that CNS-directed autoimmunity may be triggered and supported on both sides of the BBB. These data also provide a powerful approach to identify and monitor B cells in the PB that correspond to clonally amplified populations in the CNS in MS and other inflammatory states.

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