The neutralization of integrin α4(Itga4) is currently used as treatment in multiple sclerosis. Although most studies have focused on its function on lymphocyte migration to the CNS, we have uncovered the importance of Itga4 for the generation of regulatory B cells in peripheral immune organs and their control of pathogenic T cell response and CNS pathology. Our study underscores the importance of looking at the dual role of B cells in CNS autoimmunity and provides important perspectives regarding the efficacy and side effects associated with Itga4 neutralization and other B cell-targeting therapies.
Glatigny S, Wagner CA, Bettelli E. Cutting Edge: Integrin α4 Is Required for Regulatory B Cell Control of Experimental Autoimmune Encephalomyelitis. J Immunol. 2016. pii: 1502614. [Epub ahead of print]
We have heard alot about Treg cells, but there are also B regulatory cells which influence immune responsiveness and presumably because of their inhibition with Atacicept that MS worsened. Now this study suggests that the target for natalizumab controls B regulatory cells and the authos argue that this may be important in the function of natalizumab.
So whilst my mojo is rising I ask if this is the case what does natalizumab treatment tell us about B reg control of MS, because it seems that Natalizumab can do a good job in quelling relapses. Do the B regs control anti-viral responses?
Maybe we will see the same for anti-CD20 antibodies because they can make EAE better, do nothing or make it worse and this tells us that timing is critical in terms of effect and outcome.This is true of a great number of agents and so treatment is often a balance of effects.