PLX248952

GSE139671: Transcriptome analysis of in vitro generated plasmablasts dervied from Waldenstrm macroglobulinemia (WM) or heathly control B-cells

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

The ability to model WM B-cell differentiation using an in vitro system was validated in comparison to healthy cells. The stimuli used initially were CD40L and F(ab)2 anti-IgG/M, a combination which mimics T-cell dependent activation. Using these conditions, WM B-cells generated mature plasma cells that closely resemble those from healthy controls. Since WM cells harbour the characteristic gain-of-function MYD88L265P mutation, it was also of interest to determine the impact of TLR signals on the differentiation process. In contrast to the expectation of enhanced survival, WM cells exhibited a profoundly deleterious response to R848 + F(ab)2 anti-IgG/M stimulation, with a sharp decline in population from the initiation of culture and a failure to generate plasma cells. RNA sequencing was performed on material harvested from differentiating cells at day 6 of culture within the in vitro system to assess the underlying gene expression changes that accompanied the two types of stimulation. The samples consisted of 3 healthy controls with matched samples for both CD40L and R848 stimulation and a total of 6 WM samples. Examination of the transcriptomes revealed that WM plasmablasts exhibit elevated expression levels of genes associated with TLR and NF-B signaling, but reduced levels of genes associated with plasma cell re-programming. This is particularly pronounced in cells treated with the TLR7 agonist R848, suggesting an uncoupling of TLR signaling from plasma cell differentiation in WM. SOURCE: Matthew,Anthony,Care (m.a.care@leeds.ac.uk) - Bioinformatics Group The University of Leeds