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

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

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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Figure 7

Direct comparisons of IGHV germline segment usage in CSF and PB visually confirm overrepresentation of IGHV4 germline segments in MS CSF.

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Direct comparisons of IGHV germline segment usage in CSF and PB visually...
IGHV segment usage in PB (expected) plotted against usage in CSF (observed) in (A) MS and (B) OND. Proportions (%) of IGHV segments in PB were plotted against relative proportions of CSF IGHV. Each graph represents an individual patient. IGHV4-39 frequencies are in light red and IGHV4-59 or IGHV4-61 frequencies are in purple. IGHV most frequently observed in the CSF are labeled if different from IGHV4-39 and IGHV4-59 or IGHV4-61.