Again, a new report of B-cells from MS patients secreting something toxic:
Toxicity of Released B Cell Products in Multiple Sclerosis
Abstract: https://www.cambridge.org/core/journals ... EEB8659EBB
Pdf available: https://www.cambridge.org/core/services ... ocytes.pdf
OBJECTIVES/SPECIFIC AIMS:
We previously demonstrated that products released by cultured B cells from patients with Multiple Sclerosis (MS) are cytotoxic to neurons and oligodendrocytes, while minimal toxicity was observed in response to B cell secretory products from age- and sex-matched normal controls.
The goal of this proposal is to identify the range of brain cells susceptible to MS B cell-mediated cytotoxicity, to define the cytotoxic factor(s) released by MS B cells, and to determine whether particular subset(s) of MS B cells harbor the greatest pathogenic potential.
RESULTS/ANTICIPATED RESULTS:
We hypothesize that the toxicity of MS B cell products is mediated, at least in part, by extracellular vesicles, such as exosomes. We expect depletion of these exosomes from the B cell conditioned media or inhibition of their biogenesis will mitigate the observed toxicity.
Furthermore, differences in B cell-derived exosomal content, such as proteins, (mi)RNAs, or lipids, likely explain the differences in observed toxicity. Lastly, we hypothesize that memory B cells, which are enriched in the CNS of MS patients and demonstrate a more pro-inflammatory profile than naïve B cells, are responsible for the toxicity observed in supernatants of total B cells.
Toxicity of B Cell Products in Multiple Sclerosis
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