The E26 Transformation-Specific-Family Transcription Factor Spi-C is Dynamically Regulated by External Signals in B Cells
Abstract
Spi-C is an E26 transformation-specific transcription factor closely related to PU.1 and Spi-B. Spi-C has lineage-instructive functions important in antibody-generating responses, B cell development, and red pulp macrophage generation. Spi-C is inducible by heme- and NF-κB-dependent pathways in macrophages. The present research aimed to examine the regulation of Spi-C in B cells. RT-qPCR revealed that Spic expression was reduced in B cells following addition of lipopolysaccharide, anti-IgM antibodies, CD40L, or cytokines BAFF+IL-4+IL-5. Blocking proliferative signaling partially prevented downregulation of Spic. Unstimulated B cells upregulated Spic over time. To determine the mechanism of Spic regulation, we examined the Spic promoter and regulatory elements. The Spic promoter had unidirectional activity, which was reduced by mutation of a predicted NF-κB binding site. Bach2 and Spi-C formed a negative regulatory loop, repressing transcription of one another. Taken together, these data indicate that Spi-C is dynamically regulated by external signals in B cells.