title: 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.affiliation: Department of Neurology, UCSF, San Francisco, California 94158, USA. Hans-Christian.vonBuedingen@ucsf.edu
authors.forename: H-Christian
authors.initials: HC
authors.lastname: von Büdingen
authors.forename: Tracy C
authors.initials: TC
authors.lastname: Kuo
authors.forename: Marina
authors.initials: M
authors.lastname: Sirota
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: van Belle
authors.forename: Leonard
authors.initials: L
authors.lastname: Apeltsin
authors.forename: Jacob
authors.initials: J
authors.lastname: Glanville
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Cree
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Gourraud
authors.forename: Amy
authors.initials: A
authors.lastname: Schwartzburg
authors.forename: Gabriella
authors.initials: G
authors.lastname: Huerta
authors.forename: Dilduz
authors.initials: D
authors.lastname: Telman
authors.forename: Purnima D
authors.initials: PD
authors.lastname: Sundar
authors.forename: Tyler
authors.initials: T
authors.lastname: Casey
authors.forename: David R
authors.initials: DR
authors.lastname: Cox
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D001812:Blood-Brain Barrier / Q000276:immunology* / Q000473:pathology; D060965:Clonal Evolution; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000134:cerebrospinal fluid / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell