The prototypic IFN-inducible transcription factor, IRF1, not only controls inflammatory gene expression but also regulates T cell and macrophage fate specification and function. Using bone marrow chimeras (80% B6.129S2-Ighm^tm1Cgn/J [µMT] + 20% B6.129S2-Irf1^tm1Mak/J [Irf1^−/−]), we show that IRF1 expression in B cells is required for marginal zone B (MZB) cell development and T cell–independent Ab responses. Although IFNs can induce IRF1 expression in MZB precursors, deletion of the IFN-γR (C57BL/6J [B6], B6.129S7-Ifngr1^tm1Agt/J) or IFN-αR (B6[Cg]-Ifnar1^tm1Agt/J) did not affect MZB cell development. Instead, BCR and TLR signals promote IRF1 expression and nuclear translocation in MZB cell precursors. In turn, IRF1 is required for Notch2-dependent gene expression in BCR- and TLR-stimulated transitional B cells and development of the MZB cell compartment. Thus, IRF1 regulates MZB-driven T cell–independent Ab responses by regulating Notch programming in MZB precursors and facilitating commitment of these cells to the MZB lineage.



Summary

IRF1, an IFN-inducible transcription factor, is crucial for both inflammation and immune cell development. Studies using bone marrow chimeras reveal that IRF1 expression in B cells is essential for marginal zone B (MZB) cell development and T cell-independent antibody responses. While IFNs can induce IRF1, MZB cell development is driven by BCR and TLR signals, which promote IRF1 expression and nuclear translocation in MZB precursors. IRF1 then facilitates Notch2-dependent gene expression, vital for transitional B cell commitment to the MZB lineage. This research demonstrates that IRF1 regulates MZB cell fate and function by influencing Notch programming, ultimately controlling T cell-independent antibody responses.

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