The Marginal Zone B Cell Compartment and T Cell–independent Antibody Responses Are Supported by B Cell Intrinsic Expression of IRF1

作者：Jessica N. Peel, Eddie‐Williams Owiredu, Alexander F. Rosenberg, Aarón Silva-Sánchez, Troy D. Randall, John F. Kearney, Frances E. Lund · 发表于：The Journal of Immunology · 年份：2024 · DOI：10.4049/jimmunol.2300575 · 被引用次数：9 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、NF-κB Signaling Pathways

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-Ighmtm1Cgn/J [µMT] + 20% B6.129S2-Irf1tm1Mak/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-Ifngr1tm1Agt/J) or IFN-αR (B6[Cg]-Ifnar1tm1Agt/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.