Reduced Lymphocyte Longevity and Homeostatic Proliferation in Lamin B Receptor-Deficient Mice Results in Profound and Progressive Lymphopenia
- Author(s)
- Verhagen, AM; de Graaf, CA; Baldwin, TM; Goradia, A; Collinge, JE; Kile, BT; Metcalf, D; Starr, R; Hilton, DJ;
- Details
- Publication Year 2012-01-01,Volume 188,Issue #1,Page 122-134
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- The lamin B receptor (LBR) is a highly unusual inner nuclear membrane protein with multiple functions. Reduced levels are associated with decreased neutrophil lobularity, whereas complete absence of LBR results in severe skeletal dysplasia and in utero/perinatal lethality. We describe a mouse pedigree, Lym3, with normal bone marrow and thymic development but profound and progressive lymphopenia particularly within the T cell compartment. This defect arises from a point mutation within the Lbr gene with only trace mutant protein detectable in homozygotes, albeit sufficient for normal development. Reduced T cell homeostatic proliferative potential and life span in vivo were found to contribute to lymphopenia. To investigate the role of LBR in gene silencing in hematopoietic cells, we examined gene expression in wild-type and mutant lymph node CD8 T cells and bone marrow neutrophils. Although LBR deficiency had a very mild impact on gene expression overall, for common genes differentially expressed in both LBR-deficient CD8 T cells and neutrophils, gene upregulation prevailed, supporting a role for LBR in their suppression. In summary, this study demonstrates that LBR deficiency affects not only nuclear architecture but also proliferation, cell viability, and gene expression of hematopoietic cells. The Journal of Immunology, 2012, 188: 122-134.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- INNER NUCLEAR-MEMBRANE; 3-BETA-HYDROXYSTEROL DELTA(14)-REDUCTASE DEFICIENCY; MEMORY T-CELLS; BINDING-PROTEIN; IMPORTIN-BETA; GENE; MOUSE; CHROMATIN; LAMINOPATHIES; MUTATIONS
- Research Division(s)
- Cancer And Haematology; Molecular Medicine
- Publisher's Version
- https://doi.org/doi: 10.4049/jimmunol.1100942
- Terms of Use/Rights Notice
- Copyright © 2011 by The American Association of Immunologists, Inc.
Creation Date: 2012-01-01 12:00:00
Last Modified: 2014-12-23 12:03:20