title: Autoantigen induced clonal expansion in immortalized B cells from the peripheral blood of multiple sclerosis patients.
abstract: We studied Ig heavy chain (VDJ) sequences and antigen reactivity of 412 immortalized B cell lines from the peripheral blood of 10 multiple sclerosis (MS) patients, 4 clinically isolated syndrome (CIS) patients and 6 healthy controls (HCs). 78/238 (32.8%) MS and CIS B cell lines were part of 9 clonally expanded B cell populations, of which 5 were present in multiple patients. Increased VH1 gene family usage was evidenced for MS B cells, with 29.2% expressing VH1-69. Affinity maturation in MS and CIS was indicated by increased Ig VDJ mutations. Autoantibody producing B cells reactive to intracellular antigens were significantly higher in MS (25%) and CIS (28%) patients than in HCs (5%), including 3/9 expanded B cell clones. Specificity for phosphatidylcholine was observed for 1/9 B cell clones. These findings indicate clonally expanded autoreactive B cells with affinity maturation in the peripheral blood in MS and CIS.
authors.affiliation: Hasselt University, Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium.
authors.forename: Judith
authors.initials: J
authors.lastname: Fraussen
authors.forename: Kathleen
authors.initials: K
authors.lastname: Vrolix
authors.forename: Nele
authors.initials: N
authors.lastname: Claes
authors.forename: Pilar
authors.initials: P
authors.lastname: Martinez-Martinez
authors.forename: Mario
authors.initials: M
authors.lastname: Losen
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
authors.forename: Bart
authors.initials: B
authors.lastname: Van Wijmeersch
authors.forename: Mercedes
authors.initials: M
authors.lastname: Espiño
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Villar
authors.forename: Marc H
authors.initials: MH
authors.lastname: De Baets
authors.forename: Piet
authors.initials: P
authors.lastname: Stinissen
authors.forename: Veerle
authors.initials: V
authors.lastname: Somers
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000097:blood* / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002461:Cell Line, Transformed; D060966:Clonal Selection, Antigen-Mediated / Q000502:physiology*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000276:immunology / Q000473:pathology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens
keywords: Autoreactivity; B cell immortalization; Clinically isolated syndrome; Clonal B cell expansion; Complementarity determining region 3; Multiple sclerosis