Research: B cells in the brains of MSers

Epub: Von Büdingen 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.”

11 thoughts on “Research: B cells in the brains of MSers”

    1. I think they would need to reach the CSF in sufficient quantity. I think there has been an intrathecal study.

  1. This sounds promising – presumably work is being carried out to discover more along these lines? Thanks for all the updates.

    1. Look back a few days ago

  2. Is it posible that brain call for help own imuno system and calling b cells 4 help but inffection is inside of brain and b- cells cant go there , so inflamation is only secondary element of ms ? This is not theory only my thinkin

    1. Yes there are people who think this is the case that inflammation is a secondary element…VV for example, Prof G another (is this a surprise for you?)

    2. Mouse,What then is causing the neuro-degeneration if inflammation (immune) is secondary? I thought Prof G thought that EBV in B cells might be the target of the immune attack! Has he change his mind with regard to EBV as well? "This is the holy grail of MS immunologists to find what the oligoclonal bands react with". Why should we be interested in what MS immunologist think if immunology is secondary to something else? Prof Ebers has worked in the field for decades. Does he have any view on what is causing the neuro-degeneration (prior to the immune response)?

    3. Gorgeous George (Prof E) has retired.I did not say neurodegeneration is secondary to inflammation but it may be and probably is secondary to what is the initiator of the lesion. If the pre active lesions are the beginning then stress oligodendrocytes would be central, is the reactivion of viruses like HERV, or are the antibodies at the centre of this as thinks DoctorLove. If they are then EBV in B cells could be the problem and so immunology would be important.

  3. Streptococus can triger autoimune reaction wich happend in my case results where damagin my bones and hearth , image that maybe u have a infection some kind secundary symptom is body temperature and tierdness and u threat that condition with ibruprofen all the time so u erase body symptoms but not the illnes ( dr mouse i am a amateur in this field but when i look at the treatmens for ms it remind me that r very simmilar like this ) i am hopeing that im wrong about this but i think that problem of all solutions must be simple and logic , takeing dmds for ms wich lower r own imune system trigering possible cancer and other inffections and not slowing distability progresion compareing with others msers is not logic to me at all

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