Notch2 Signaling Induces Trans-differentiation of Follicular to Marginal Zone B Cells

Follicular B (FoB) and marginal zone B (MZB) cells are two functionally and spatially distinct mature B cell populations in the spleen. FoB and MZB cells originate from a fate decision event in immature transitional B cells upon splenic influx. Various signaling pathways regulate the differentiation processes into these two lineages. Considering the strong lineage instructive potency of Notch2 signaling in transitional B cells we asked whether activation of Notch2 is able to induce trans-differentiation of mature FoB towards MZB cells. By using a system allowing for inducible activation of Notch2, we show here for the first time that Notch2 signaling is sufficient to re-program mature FoB into bona fide MZB cells regarding to their surface phenotype, localization, immunological function and transcriptome. Thus, our data demonstrate a remarkable plasticity between mature FoB and MZB cells that switch lineage upon a singular signaling event, the activation of Notch2.