Splenic fibroblasts control marginal zone B cell movement and function via two distinct Notch2-dependent regulatory programs

IF 25.5 1区医学 Q1 IMMUNOLOGY

Immunity Pub Date : 2024-12-27 DOI:10.1016/j.immuni.2024.12.003

Anneka Allman, Brian T. Gaudette, Samantha Kelly, Nagham Alouche, Léolène J. Carrington, Eric Perkey, Joshua D. Brandstadter, Riley Outen, Ashley Vanderbeck, Katlyn Lederer, Yeqiao Zhou, Robert B. Faryabi, Tanner F. Robertson, Janis K. Burkhardt, Anastasia Tikhonova, Iannis Aifantis, Leonardo Scarpellino, Ute Koch, Freddy Radtke, Mechthild Lütge, Ivan Maillard

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Abstract

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.

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来源期刊

Immunity 医学-免疫学

CiteScore

49.40

自引率

2.20%

发文量

205

审稿时长

6 months

期刊介绍： Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.