TY - JOUR AU - von Büdingen, H.-Christian AU - Kuo, Tracy C. AU - Sirota, Marina AU - van Belle, Christopher J. AU - Apeltsin, Leonard AU - Glanville, Jacob AU - Cree, Bruce A. AU - Gourraud, Pierre-Antoine AU - Schwartzburg, Amy AU - Huerta, Gabriella AU - Telman, Dilduz AU - Sundar, Purnima D. AU - Casey, Tyler AU - Cox, David R. AU - Hauser, Stephen L. T1 - B cell exchange across the blood-brain barrier in multiple sclerosis PY - 2012/12/03/ AB - 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI63842 VL - 122 IS - 12 UR - https://doi.org/10.1172/JCI63842 SP - 4533 EP - 4543 PB - The American Society for Clinical Investigation ER -