Back to Search
Start Over
B-cell lymphopoiesis is regulated by cathepsin L
- Source :
- PLoS ONE, Vol 8, Iss 4, p e61347 (2013), PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- Cathepsin L (CTSL) is a ubiquitously expressed lysosomal cysteine peptidase with diverse and highly specific functions. The involvement of CTSL in thymic CD4+ T-cell positive selection has been well documented. Using CTSL(nkt/nkt) mice that lack CTSL activity, we have previously demonstrated that the absence of CTSL activity affects the homeostasis of the T-cell pool by decreasing CD4+ cell thymic production and increasing CD8+ thymocyte production. Herein we investigated the influence of CTSL activity on the homeostasis of peripheral B-cell populations and bone marrow (BM) B-cell maturation. B-cell numbers were increased in lymph nodes (LN), spleen and blood from CTSL (nkt/nkt) mice. Increases in splenic B-cell numbers were restricted to transitional T1 and T2 cells and to the marginal zone (MZ) cell subpopulation. No alterations in the proliferative or apoptosis levels were detected in peripheral B-cell populations from CTSL (nkt/nkt) mice. In the BM, the percentage and the absolute number of pre-pro-B, pro-B, pre-B, immature and mature B cells were not altered. However, in vitro and in vivo experiments showed that BM B-cell production was markedly increased in CTSL (nkt/nkt) mice. Besides, BM B-cell emigration to the spleen was increased in CTSL (nkt/nkt) mice. Colony-forming unit pre-B (CFU pre-B) assays in the presence of BM stromal cells (SC) and reciprocal BM chimeras revealed that both BM B-cell precursors and SC would contribute to sustain the increased B-cell hematopoiesis in CTSL (nkt/nkt) mice. Overall, our data clearly demonstrate that CTSL negatively regulates BM B-cell production and output therefore influencing the homeostasis of peripheral B cells.
- Subjects :
- Proteomics
CD4-Positive T-Lymphocytes
B Cells
Cathepsin L
lcsh:Medicine
Apoptosis
Mice
Bone Marrow
Pathology
Homeostasis
Lymphoid Organs
lcsh:Science
Mice, Knockout
Spectrometric Identification of Proteins
Multidisciplinary
biology
Lymphopoiesis
Stem Cells
Marginal zone
Thymocyte
Haematopoiesis
medicine.anatomical_structure
Medicine
Immunohistochemical Analysis
Research Article
Histology
Stromal cell
Immune Cells
Immunology
B-Lymphocyte Subsets
Bone Marrow Cells
Spleen
Diagnostic Medicine
medicine
Animals
Biology
B cell
Cell Proliferation
Precursor Cells, B-Lymphoid
lcsh:R
Molecular biology
Gene Expression Regulation
Immune System
Immunologic Techniques
biology.protein
Clinical Immunology
lcsh:Q
Lymph Nodes
Biomarkers
General Pathology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....652e8c1f01f5446bee57895a91f1b55b