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B cell exchange across the blood-brain barrier in multiple sclerosis.

H.-Christian von Büdingen,Tracy C. Kuo,M. Sirota,Christopher J van Belle,Leonard Apeltsin,J. Glanville,B. Cree,P. Gourraud,Amy Schwartzburg,Gabriella Huerta,D. Telman,P. Sundar,Tyler Casey,D. Cox,S. Hauser

Published 2012 in Journal of Clinical Investigation

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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