Friday, 16 December 2016

B cells expand in the CNS

Lehmann-Horn K, Wang SZ, Sagan SA, Zamvil SS, von B├╝dingen HC. B cell repertoire expansion occurs in meningeal ectopic lymphoid tissue. JCI Insight. 1(20):e87234.

Ectopic lymphoid tissues (ELT) can be found in multiple sclerosis (MS) and other organ-specific inflammatory conditions. Whether ELT in the meninges of central nervous system (CNS) autoimmune disease exhibit local germinal center (GC) activity remains unknown. (Not really true....there is ample evidence that B cell aggregates do not always have a germinal centre structure...but this sentence means that this is why we did the study and the referee doesn't know the literature or is afraid to say it)
In an experimental autoimmune encephalomyelitis model of CNS autoimmunity, we found activation-induced cytidine deaminase, a GC-defining enzyme, in meningeal ELT (mELT) densely populated by B and T cells. To determine GC activity in mELT, we excised meningeal lymphoid aggregates using laser capture microscopy and evaluated B cell repertoires in mELT and secondary lymphoid organs by next-generation immune repertoire sequencing. We found immunoglobulin heavy chain variable region sequences that were unique to mELT and had accumulated functionally relevant somatic mutations, together indicating localized antigen-driven affinity maturation. Our results suggest that B cells in mELT actively participate in CNS autoimmunity, which may be relevant to mELT in MS and ELT in other chronic inflammatory conditions.
  Germinal centres in B cell follicles are easy to see in histology, 
                                  Do they occur in EAE?

In this study they find B cell aggregates and find that the antibodies produced by these B cells have demonstrated immune activation and suggest local accumulation of clones not in abundance in lymph glands. The inference is that they play a part in the disease process. This study implies B cell follicles are part of the problem in MS. This is because B cells are now the problem in MS, because CD20-depleting antibodies inhibit MS

However, EAE is mediated by T cells..let's not kid ourselves otherwise.  

Do B cell aggregates always occur in EAE?...No. 

Do they occur?...Yes. Are they germinal centres?....No.

However, is this chicken or is this egg...and I think is probably chicken because the same authors have shown that you don't need B cells for some forms of EAE.  Do B cells contribute to pathology in EAE......absolutely.


In EAE, we know the target antigen..in this example it is MOG, but in MS when people look at the B cell repertoire then the antibodies do not react to myelin, but often intra-cellular proteins. 

One example is neurofilament and this is liberated as a consequence of damage. You can make antibodies to this, but this is not as an initial cause of disease. 

Does this impact on clinical course...... yes

Does it have to mean local activation in the CNS maybe ...maybe not, many on the aggregates in EAE, I have seen do not appear to have dividing cells in them so they may not be produced locally, just locally accumulated and many of them do not contain plasma cells.

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