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B cell exchange across the blood-brain barrier in multiple sclerosis
H.-Christian von Büdingen, … , David R. Cox, Stephen L. Hauser
H.-Christian von Büdingen, … , David R. Cox, Stephen L. Hauser
Published November 19, 2012
Citation Information: J Clin Invest. 2012;122(12):4533-4543. https://doi.org/10.1172/JCI63842.
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Research Article Neuroscience Article has an altmetric score of 27

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

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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.

Authors

H.-Christian von Büdingen, 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

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B cell clones are shared between CSF and PB in subjects with CSF IgG exp...

B cell clones are shared between CSF and PB in subjects with CSF IgG expression


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ISSN: 0021-9738 (print), 1558-8238 (online)

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