Friday, 24 May 2013

B cells accumulation in MS due to failure B cell tolerance

Epub: Kinnunen et al. Specific peripheral B cell tolerance defects in patients with multiple sclerosis. J Clin Invest. 2013. doi:pii: 68775. 10.1172/JCI68775.

Multiple sclerosis (MS) is a genetically mediated autoimmune disease of the central nervous system. B cells have recently emerged as major contributors to disease pathogenesis, but the mechanisms responsible for the loss of B cell tolerance in patients with MS are largely unknown. In healthy individuals, developing autoreactive B cells are removed from the repertoire at 2 tolerance checkpoints during early B cell development. Both of these central and peripheral B cell tolerance checkpoints are defective in patients with rheumatoid arthritis (RA) and type 1 diabetes (T1D). Here, we found that only the peripheral, but not the central, B cell tolerance checkpoint is defective in patients with MS.

We show that this specific defect is accompanied by increased activation and homeostatic proliferation of mature naive B cells. Interestingly, all of these MS features parallel defects observed in FOXP3-deficient IPEX patients, who harbor nonfunctional Tregs. We demonstrate that in contrast to patients with RA or T1D, bone marrow central B cell selection in MS appears normal in most patients. In contrast, patients with MS suffer from a specific peripheral B cell tolerance defect that is potentially attributable to impaired Treg function and that leads to the accumulation of autoreactive B cell clones in their blood.



Tolerance is the process by which white blood cells become educated not to react with your own body. This process first occurs in the bone marrow for B cells and the Thymus for T cells. This "central tolerance". If this does not occur there is also the chance of "peripheral tolerance" in the blood. These stop autoimmunity occurring.. In this study it is claimed that B cell tolerance in the blood fails and leads to the accumulation of potentially damaging B cells. 

Is this the reason why MSers show enhanced B cell respponses after Alemtuzumab treatment.

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