Interferon betas augment B cell function

Schubert RD, Hu Y, Kumar G, Szeto S, Abraham P, Winderl J, Guthridge JM, Pardo G, Dunn J, Steinman L, Axtell RC.IFN-β Treatment Requires B Cells for Efficacy in Neuroautoimmunity.
J Immunol. 2015 Feb. pii: 1402029. [Epub ahead of print]
IFN-β remains the most widely prescribed treatment for relapsing remitting multiple sclerosis. Despite widespread use of IFN-β, the therapeutic mechanism is still partially understood. Particularly, the clinical relevance of increased B cell activity during IFN-β treatment is unclear. We show that IFN-β pushes some B cells into a transitional, regulatory population that is a critical mechanism for therapy. IFN-β treatment increases the absolute number of regulatory CD19+, CD24++, CD38++ transitional B cells in peripheral blood relative to treatment-naive and Copaxone-treated patients. In addition, we found that transitional B cells from both healthy controls and IFN-β-treated MS patients are potent producers of IL-10, and that the capability of IFN-β to induce IL-10 is amplified when B cells are stimulated. Similar changes are seen in mice with experimental autoimmune encephalomyelitis. IFN-β treatment increases transitional and regulatory B cell populations, as well as IL-10 secretion in the spleen. Furthermore, we found that IFN-β increases autoantibody production, implicating humoral immune activation in B cell regulatory responses. Finally, we demonstrate that IFN-β therapy requires immune-regulatory B cells by showing that B cell-deficient mice do not benefit clinically or histopathologically from IFN-β treatment. These results have significant implications for the diagnosis and treatment of relapsing remitting multiple sclerosis.
When I was a snip of a lad starting out in science, my old boss thought that suppressor B cells were a large part of drug responsiveness. However, T cell suppressors and regulators were the flavour and I forgot about them like the rest of the immunological world. However thirty years on maybe it time for them to resurface. ProfG has been making the case for the importance of B cells in MS, other people ignore this idea and plough on with the T cell hypothesis and eat the black swan for breakfast.

However B cells ain't all bad and this study suggest that B cells are important for the action of beta interferon, not by inhibiting them but by producing B  cells, regulatory B cells tha produce IL-10 which is a T cell regulatory cytokine (a B cell helping cytokine). They do the studies in mice and the same thing happens but it shows that it increases autoantigen antibodies, and this is a good thing? Whilst we have published studies that shows some autoantibodies can be beneficial a lot of studies indicate that antibodies against myelin and nerve protein is a bad thing. If you get rid of B cells beta interferon doesn't work and this hasimplications for therapy, however we have to point out that beta interferons are low efficacy DMT (for the MS population some MSers do well on them).

This study suggests what we already know that some B cells are inhibitory to the disease process whereas some B cells are bad for the disease process. Anti-CD20 B cell depletion therapy blocks relapsing MS, Atacicept which was also designed to inhibit B cells actually made MS worse. 

So anti-CD19 could make MS worse because it could get rid of the CD19+ transional cells....but does it?

Should ProfG be quaking as he is a PI on this trial or will he be smiling.  The trial of MEDI 551 trial an anti CD19 in MS should finish around his month,I don't think it got stopped so I guess there wasn't worsening, so should get presented his year.

CoI ProfG multiple

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