Stage Specific Non-coding RNA Expression Patterns During in vitro Human B Cell Differentiation into Antibody Secreting Plasma Cells

The differentiation of activated B cells into antibody secreting plasma cells (PCs) is governed by a strict regulatory network that results in expression of specific transcriptomes along the continuum. In vitro models resulting in PCs that are phenotypically identical to the in vivo state permit investigation of molecules, transcripts, pathways, and metabolomes not previously identified in the differentiation process. We used an in vitro system and RNA-seq to identify protein-coding and non-coding RNA (ncRNA) transcripts expressed in human resting and activated B cells, and PCs. Analysis of immunoglobulin (Ig) transcripts showed that the repertoire was not skewed, and that memory B cells preferentially expanded and differentiated into PCs. Of interest, we identified more than 980 differentially expressed ncRNA transcripts displaying stage-specific patterns of increased or decreased expression across differentiation some of which are known to target transcription, proliferation, cytoskeletal, autophagy and proteasome pathways. Interestingly, ncRNAs located within Ig loci may be targeting both Ig and non-Ig related transcripts. ncRNAs associated with B cell malignancies were also identified in this model. Taken together, this system provides a platform to study the detailed role of specific ncRNAs in B cell differentiation and altered expression of those ncRNAs involved in B cell malignancies. Transcriptome profiles from 3 human B cell differentiation experiments. RNA-seq was performed from resting cells (Day 0), Plasmablasts (Day 4) and in vitro Plasma Cells (IVPCs, Day 10).