Childhood MS shows us that Memory B cells are Important in MS

Schwarz A, Balint B, Korporal-Kuhnke M, Jarius S, von Engelhardt K, F├╝rwentsches A, Bussmann C, Ebinger F, Wildemann B, Haas J. B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2016;4(1):e309

OBJECTIVE:

To comparatively assess the B-cell composition in blood and CSF of patients with paediatric-onset multiple sclerosis (pedMS) and adult-onset multiple sclerosis (adMS).

METHODS:

In this cross-sectional study, we obtained blood and CSF samples from 25 patients with pedMS (8-18 years) and 40 patients with adMS (23-65 years) and blood specimens from 66 controls (1-55 years). By using multicolour flow cytometry, we identified naive, transitional, isotype class-switched memory, non-switched memory, and double-negative memory B-cell subsets as well as plasmablasts (PB) and terminally differentiated plasma cells (PC). Flow cytometric data were compared to concentrations of B-cell-specific cytokines in serum and CSF as determined by ELISA.

RESULTS:

Frequencies of circulating naive B-cells decreased with higher age in controls but not in patients with multiple sclerosis (MS). B-cell patterns in CSF differed between pedMS and adMS with an acute relapse: in pedMS-derived CSF samples, high frequencies of non-switched memory B cells and PB were present, whereas class-switched memory B cells and PC dominated in the CSF of patients with adMS. In pedMS, PB were also elevated in the periphery. Accumulation of PB in the CSF correlated with high intrathecal CXCL-13 levels and augmented intrathecal synthesis of immunoglobulin G and immunoglobulin M.

CONCLUSIONS:

We demonstrate distinct changes in intrathecal B-cell homeostasis in patients with pedMS during active disease, which differ from those in adults by an expansion of plasmablasts in blood and CSF and similarly occur in prototypic autoantibody-driven autoimmune disorders. This emphasizes the particular importance of activated B-lymphocyte subsets for disease progression in the earliest clinical stages of MS.

This provides further evidence for a role of B cell memory in MS. 

The authors are not looking for anything other than B cells and so they don't really focus on the memory B cell, but if you think that this population harbours what drives MS then the data jumps at you.

First thing as you get older and encounter more things the immune system is interested in the number of naive (Mature) B cells drops to be replaced with memory B cells.You have to remember these are percentages so if the naive (mature) cells go up memory cells must go down and vice versa, the best way to do this is to calculate absolute numbers then you can see if there are more or less cells.

However, here they look at the B cell populations in young and adult pwMS and compared to health in the young it is clear that people with MS have more B memory cells in their blood.

In relapse the percentage of memory cells go down. 

Is this because they are off into the CNS?.

The memory cells (CD19+, CD27+) make up 66%/75.9% (Paedatric/adult) of B cells in CSF compared to 30.1%/33.2% in the remission blood. 


So memory B cells are being recruited to or they are retained with in the CNS in MS. 

The data in the CSF may create some complexity as it looks like young and adult memory pool is not quite the same, but we have to remember, it is unlikely that every cell found in CNS is pathogenic, many get drawn in because of the adhesion molecules/chemokines and there may be ectopoic resident cells in CNS contributing to the pool.

So the question is which memory B cell subset is causing the damage? However, is it the memory cell is more important than the type of memory cell, which could support the EBV idea as they will get infected in the unswitched (IgD+) state and this will persist in the switched B (IgD-) cells. 

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