Transcriptional Control of Mature B Cell Fates

The mature naïve B cell repertoire consists of three well-defined populations: B1, B2 (follicular B, FOB), and marginal zone B (MZB) cells. FOB cells are the dominant mature B cell population in the secondary lymphoid organs and blood of both humans and mice. The driving forces behind mature B lineage selection have been linked to B cell receptor (BCR) signaling strength and environmental cues, but how these fate-determination factors are transcriptionally regulated remains poorly understood. We summarize emerging data on the role of transcription factors (TFs) - particularly the ETS and IRF families - in regulating MZB and FOB lineage selection. Indeed, genomic analyses have identified four major groups of target genes that are crucial for FOB differentiation, revealing previously unrecognized pathways that ultimately determine biological responses specific to this lineage.