UC San Diego

As B cells develop from hematopoietic stem cell to mature- B cell, a large network of transcription factors and global chromosomal changes must occur in a well-timed manner. If those events fail to progress properly, disease states may occur in the form of autoimmune disease, immunodeficiency, leukemia or lymphoma. Understanding the individual factors at each developmental stage is critical in understanding disease states and, eventually, the best way to treat them. Although we have an understanding of transcription factors and chromosomal changes, it has only been until recent technological advances that we have been able to identify a new type of factor that is involved in B cell development. With next-generation sequencing (NGS), we have been able to identify 403 long noncoding intergenic RNAs that are developmentally regulated between the critical stages of B cell specification to commitment (i.e.: pre-pro-B to pro-B cell stage). We further investigate global disruption to gene patters when twelve lincRNAs are reduced in transcript expression through shRNA-mediated silencing followed by RNA-Seq. Many of the genes disrupted were critical to pathways involving disease states such as B cell Receptor pathway, Antigen Presentation pathway, Autoimmune Thyroid Disease pathway, Allograft Rejection pathway, and Primary Immunodeficiency. We then focus on one transcript, lincRNA-E1, which showed a disruption of genes involved in the B Cell Receptor pathway and genes involved in hematopoiesis including FOS, CD79a, and CD79b. We confirmed that lincRNA-E1 is developmentally regulated and tissue specific, restricted to hematopoietic lineages. In an in vitro differentiation, silencing expression of lincRNA-E1 leads to an increase in CD19+B220+ pro-B cells. Taken together, we have identified a novel lincRNA-E1 that plays a role is early B cell development