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

J Bankoti, L Apeltsin, SL Hauser, S Allen… - Annals of …, 2014 - Wiley Online Library
J Bankoti, L Apeltsin, SL Hauser, S Allen, ME Albertolle, HE Witkowska, HC von Büdingen
Annals of neurology, 2014Wiley Online Library
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 …
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
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