In multiple sclerosis, oligoclonal bands connect to peripheral B-cell responses

• Published in: Annals of neurology Vol. 75; no. 2; pp. 266 - 276
• Main Authors: Bankoti, Jaishree, Apeltsin, Leonard, Hauser, Stephen L., Allen, Simon, Albertolle, Matthew E., Witkowska, H. Ewa, von Büdingen, H.-Christian
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.02.2014; Wiley Subscription Services, Inc; BlackWell Publishing Ltd
• Subjects: Adult; Antigens; B-Lymphocytes - immunology; Blood-brain barrier; Female; Gene Expression Profiling; Humans; Immune system; Isoelectric Focusing; Male; Mass Spectrometry; Multiple Sclerosis - blood; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - immunology; Oligoclonal Bands - cerebrospinal fluid; Proteome; Young Adult
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.24088

Objective To determine to what extent oligoclonal band (OCB) specificities are clonally interrelated and to what degree they are associated with corresponding B‐cell responses in the peripheral blood (PB) of multiple sclerosis (MS) patients. Methods Mass‐spectrometric proteomic analysis of isoelectric focused (IEF) cerebrospinal fluid (CSF) immunoglobulin G (IgG) was used in combination with next‐generation deep‐immune repertoire sequencing of PB and CSF IgG heavy chain variable regions from MS patients. Results We find evidence for ongoing stimulation and maturation to antibody‐expressing B cells to occur primarily inside the central nervous system (CNS) compartment. B cells participating in OCB production can also be identified in PB; these cells appear to migrate across the blood–brain barrier and may also undergo further antigen stimulation in the periphery. In individual patients, different bands comprising OCBs are clonally related. Interpretation Our data provide a high‐resolution molecular analysis of OCBs and strongly support the concept that OCBs are not merely the terminal result of a targeted immune response in MS but represent a component of active B cell immunity that is dynamically supported on both sides of the blood‐brain barrier. Ann Neurol 2014;75:266–276