Splenic fibroblasts control marginal zone B cell movement and function via two distinct Notch2-dependent regulatory programs Journal Article
| Authors: | Allman, A.; Gaudette, B. T.; Kelly, S.; Alouche, N.; Carrington, L. J.; Perkey, E.; Brandstadter, J. D.; Outen, R.; Vanderbeck, A.; Lederer, K.; Zhou, Y.; Faryabi, R. B.; Robertson, T. F.; Burkhardt, J. K.; Tikhonova, A.; Aifantis, I.; Scarpellino, L.; Koch, U.; Radtke, F.; Lütge, M.; De Martin, A.; Ludewig, B.; Tveriakhina, L.; Gossler, A.; Mosteiro, L.; Siebel, C. W.; Gómez Atria, D.; Luther, S. A.; Allman, D.; Maillard, I. |
| Article Title: | Splenic fibroblasts control marginal zone B cell movement and function via two distinct Notch2-dependent regulatory programs |
| 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. © 2024 Elsevier Inc. |
| Keywords: | controlled study; unclassified drug; nonhuman; animal cell; mouse; animal tissue; cell function; gene expression; cell growth; spleen; animal experiment; protein; cell motion; b lymphocyte; b cell lymphoma; chemotaxis; myc protein; cell migration; fibroblast; cell size; b cells; notch2 receptor; notch; marginal zone; notch signaling; fibroblastic reticular cells; human; male; female; article; memory b lymphocyte; delta like1 protein; sphingosine 1 phosphate receptor |
| Journal Title: | Immunity |
| Volume: | 58 |
| Issue: | 1 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2025-01-14 |
| Start Page: | 143 |
| End Page: | 161.e8 |
| Language: | English |
| DOI: | 10.1016/j.immuni.2024.12.003 |
| PUBMED: | 39731910 |
| PROVIDER: | scopus |
| PMCID: | PMC11735314 |
| DOI/URL: | |
| Notes: | Article -- MSK corresponding author is Ivan Maillard -- Source: Scopus |
