Forced Notch2 signaling instructs TLR and BCR responsiveness in B cells [RNA-Seq]

Marginal zone (MZ) B cells optimize protection against blood-borne bacteria by rapidly producing plasma cells in response to Toll-like Receptor (TLR) ligands. Here, we demonstrate that forced Notch2 instructs this responsiveness for Notch2-independent follicular B cells. Upon stimulation with either TLR4 ligand LPS or B cell receptor crosslinking via anti-IgM, access to Notch2 ligands promoted early transcriptional changes to numerous activation programs. These changes include augmenting TLR response programs, early and late mitotic pathways, and key cell growth and protein secretion pathways critical for plasma cell differentiation. We conclude that t uniquely robust hyper-responsiveness can be ascribed to any B cell with access to Notch2 ligands.