Reduced Lymphocyte Longevity and Homeostatic Proliferation in Lamin B Receptor-Deficient Mice Results in Profound and Progressive Lymphopenia
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
WEHI Research Division(s)
Cancer And Haematology; Molecular Medicine
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
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