B cell exchange across the blood-brain barrier in multiple sclerosis.
von Budingen, H.-Christian 1; Kuo, Tracy C. 2; Sirota, Marina 2; van Belle, Christopher J. 1; Apeltsin, Leonard 1; Glanville, Jacob 3; Cree, Bruce A. 1; Gourraud, Pierre-Antoine 1; Schwartzburg, Amy 1; Huerta, Gabriella 2; Telman, Dilduz 2; Sundar, Purnima D. 2; Casey, Tyler 1; Cox, David R. 2; Hauser, Stephen L. 1
[Article]
Journal of Clinical Investigation.
122(12):4533-4543, December 3, 2012.
(Format: HTML, PDF)
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.
Copyright (C) 2012 The American Society for Clinical Investigation, Inc.