Immunity · 2024
Splenic fibroblasts control marginal zone B cell movement and function via two distinct Notch2-dependent regulatory programs.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Allman Anneka, Gaudette Brian T, Kelly Samantha, Alouche Nagham, Carrington Léolène J, Perkey Eric, Brandstadter Joshua D, Outen Riley, Vanderbeck Ashley, Lederer Katlyn, Zhou Yeqiao, Faryabi Robert B, Robertson Tanner F, Burkhardt Janis K, Tikhonova Anastasia, Aifantis Iannis, Scarpellino Leonardo, Koch Ute, Radtke Freddy, Lütge Mechthild, De Martin Angelina, Ludewig Burkhard, Tveriakhina Lena, Gossler Achim, Mosteiro Lluc, Siebel Christian W, Gómez Atria Daniela, Luther Sanjiv A, Allman David, Maillard Ivan
Аннотация
Innate-like splenic marginal zone (MZ) B (MZB) cells play unique roles in immunity due to their rapid responsiveness to blood-borne microbes. How MZB cells integrate cell-extrinsic and -intrinsic processes to achieve accelerated responsiveness is unclear. We found that Delta-like1 (Dll1) Notch ligands in splenic fibroblasts regulated MZB cell pool size, migration, and function. Dll1 could not be replaced by the alternative Notch ligand Dll4. Dll1-Notch2 signaling regulated a Myc-dependent gene expression program fostering cell growth and a Myc-independent program controlling cell-movement regulators such as sphingosine-1 phosphate receptor 1 (S1PR1). S1pr1-deficient B cells experienced Notch signaling within B cell follicles without entering the MZ and were retained in the spleen upon Notch deprivation. Key elements of the mouse B cell Notch regulome were preserved in subsets of human memory B cells and B cell lymphomas. Thus, specialized niches program the poised state and patrolling behavior of MZB cells via conserved Myc-dependent and Myc-independent Notch2-regulated mechanisms.