Research: B cells in the brains of MSers

Epub: Von B├╝dingen et al. B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Invest. 2012 Nov 19. doi:pii: 63842. 10.1172/JCI63842.

Background: In 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. 
Objective: To applied deep repertoire sequencing of IgG heavy chain variable region genes (IgG-VH) in paired cerebrospinal fluid and PB samples from MSers and people with other neurological diseases to identify related B cells that are common to both compartments. 
Results: For the first time to their knowledge, the investigator's found that a restricted pool of clonally related B cells participated in robust bidirectional exchange across the BBB. Some clusters of related IgG-VH (variable part of the heavy chain of IgG) 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. 
Conclusion: 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.


Clusters of B cells expressing identical and/or related IgG-VH are shared between CSF and Blood


"For the first time this study identified related or identical B cells on both sides of the BBB. Clustering of related genes coding the variable part of the heavy chain of immunoglobulin G (IgG-VH) or antibody target binding. Closely related B cells, existed on both sides of the blood-brain-barrier, were not exclusively found in MSers but were also detected in some people with other neurological diseases. In healthy state B cell migration across the BBB is limited but is initiated or magnified during the course of diverse CNS disorders. In MS, this connection may be distinctive in 2 important ways: CSF B cell repertoires are biased in their usage of certain IGHV germline segments (maybe suggesting certain common targets), and there is strong evidence for robust B cell activation. These results lend support to the concept that highly active immune responses involving a select pool of B cells are centrally involved in the immunopathology of MS. The next stage will be to identify the targets of these antibodies."

This is the holy grail of MS immunologists to find what the oligoclonal bands react with. Finding this out will probably identify the cause of MS. Despite this this data supports the therapeutic strategy of targeting B cells with monoclonal antibodies; either CD20 and CD19."

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