Kim H, Schneider M, Raach Y, Karypidis P, Roux J, Perdikaris G, Holdermann S, Kulsvehagen L, Lecourt AC, Narr K, Sankowski R, Diebold M, Bartoszek-Kandler E, Kapfhammer JP, Zimmer G, Pröbstel AK, Prinz M, Kappos L, Sanderson NSR, Derfuss T. Myelin antigen capture in the CNS by B cells expressing EBV latent membrane protein 1 leads to demyelinating lesion formation. Cell. 2026 Jan 13:S0092-8674(25)01480-1
The efficacy of B cell depletion therapies, and their association with Epstein-Barr virus (EBV), implicate B cells in the pathogenesis of multiple sclerosis (MS). In mice, we observed that viral infections induce infiltration of B cells into the brain, independent of phenotype and specificity, and that myelin-reactive B cells then capture antigens directly from parenchyma. (Over 50 years ago it was demonstrated that activated cells migrate more into tissues irrespective of their target…find it they stay don’t find it they leave or more likely die as we continually make cells) Trafficking of these antigen-loaded B cells (It was shown years ago that B cells are antigen presenting cells) to draining lymph nodes was not observed (So B cells don’t leave fine but it was suggested decades ago that the antigens can), and without T cell help, antigen-capturing B cells die rapidly (It was known when I am an amoeba that B cells have a limited lifespan and that something has to be given to keep them alive. This keeps them alive but also they differentiate towards being memory or antibody making cells. The two main features that are requuired is signallying from the B cell antigen receptor and the second signal is the CD40 checkpoint. These need to be stimulated by antigen or by CD40Ligand, but it has been known for years that EBV creates these survival signals. The mimic the signalling from the B cell receptor by making a molecule called latent membrane protein two, they also mimic the signal from the CD40 receptor by making Latent membrane protein one, in addition they make a viral interleukin 10 that helps B cells grow and differentiate because IL-10 is a B cell grow survival factor. They also make B cells produce CD40 ligand to give more signalling which allows B cells to be activated differentiate and survive without the need for a specific antigen signal or the requirement for cells expressing CD40 ligand….We suggested about a decade ago that this could be a driver for autoimmunity. CD40L signaling or EBV latent membrane protein 1 (LMP1) can override this checkpoint, leading to B cell-receptor- and/or antibody-dependent inflammatory demyelination (So NSS). Myelin-reactive B cells were identified in the healthy human B cell repertoire (This has been known and shown for decades. It is obvious that these can be found because one can drive them to be even more common..you could not have EAE is you didnt have reactive cells in the first place), and expression of LMP1 was observed in the brains of a subset of MS patients. These observations can explain the dependency of disease incidence on prior EBV infection, and the increased risk associated with brain infections, and suggest possible treatment strategies (There you go… Great minds think alike however you can have as many ideas that you like, showning the evidence is another thing…This process would allow EBV to be at the centre of alot of different autoimmunities)
Source: multiple-sclerosis-research.org