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Myelin antigen capture in the CNS by B cells expressing EBV latent membrane protein 1 leads to demyelinating lesion formation [RNA-Seq]

GSE308212 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2026/01/13 Platform GPL24247
Summary
The efficacy of B cell depletion therapies, and association with the B lymphotropic Epstein- Barr virus (EBV) implicate B cells in the demyelinating autoimmune disease multiple sclerosis. After observing myelin-reactive B cells in the naïve human repertoire, we studied how such cells behave in the central nervous system. In mice, viral infections induce infiltration of B cells independent of phenotype and specificity into the otherwise lymphocyte-poor brain, and myelin-reactive B cells then capture antigen directly from parenchyma. Trafficking of these antigen-loaded B cells to draining lymph nodes was not observed, and without T cell help, antigen-capturing B cells die rapidly. CD40L signaling or EBV latent membrane protein 1 (LMP1) can override this checkpoint, leading to in situ plasma cell differentiation and antibody-mediated, demyelinating lesion formation. These observations explain the dependency of disease incidence on prior EBV infection, and the increased risk associated with brain infections, and suggest possible treatment strategies.
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Also filed as BioProject PRJNA1329221 and SRA study SRP620777. Searching any of these in the dataset finder brings you back here.

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