Research: B cells and Demyelination

EpubLisak et al. Secretory products of multiple sclerosis B cells are cytotoxic to oligodendroglia in vitro.J Neuroimmunol. 2012 Mar 28.

B cells are important in the pathogenesis of MS and some of the effects are not dependent on maturation of B cells into immunoglobulin (Ig) producing plasmablasts and plasma cells (cell factories that make antibodies). B cells present antigen (messages to activate T cells), activate T cells, and are involved in immunoregulation and cytokine secretion (cytokines are the messages immune cells use to talk to each other).

To determine if B cells from MSers secrete products that have deleterious effects on glial cells (an oligodendrocyte the cell that makes myelin is one type of glial cell) not mediated by antibodies, and to compare effects with secretory products of normal controls (NC), we isolated B cells from 7 MSers RRMS and 4 NC. The effects of B cell supernatants (fluid from the B cell culture) on oligodendrocytes could be direct and/or indirect involving either microglia  (scavenger cells) and/or astrocytes (another glial cell). The identity of the toxic factor(s) is as yet unknown. Thus we have demonstrated that B cells from patients with RRMS but not NC secrete one or more factors toxic to 
oligodendrocytes.  It is possible that such factors produced by peripheral blood B cells when within the CNS could contribute to demyelination in MSers.

“The results say it all, which indicate that immune cells can damage oligodendrocytes. These damaging molecules do not have to be antibodies that B cells produce, but can be other soluble factors produced by B cells. This means that B cells would not need to be near the oligodendrocyte to damage them. This must be born in mind when thinking of the work of Prineas and colleagues that suggested oligodendrocyte damage in the apparent absence of immune cells.”

4 thoughts on “Research: B cells and Demyelination”

  1. To be exact:The researchers proved that human B cells from RRMS patients killed more rat oligodendrocytes in a testing tube (57%) than human B cells from normal controls (7%). The question remains whether this can also happen in the human brain. On the other hand B cells are flowing in the bloodstream and are never still. Yet, the area of dead oligos is rather confined and specific. This means they would have to stop their motion and secrete their "venom" through the BBB which is not the most plausible idea. Let alone the preference of lesions to form in the periventricular area around large veins with brisk blood flow.

  2. VV why is it implausible? These secretory products could be small molecules that can pass through the BBB. There is no need for B cells to stop their motion. They just have to release these substances.

  3. Once the substances are released, they are all over flowing in the blood. If they are capable of crossing the BBB they should affect an extended part of the CNS along the venous pathway. Moreover, this affection should be seen throughout the venous system and especially where the flow speed of the blood is low, that is the post capillary space. Yet, the form and the topography of the lesions in MS is very different and provides no support for this claim: the site of apoptotic oliodendrocytes is not diffuse and the lesions themselves do not appear anywhere in the CNS, but have some favourite places.

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