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- Title
p53-mediated apoptosis prevents the accumulation of progenitor B cells and B-cell tumors.
- Authors
Slatter, T. L.; Ganesan, P.; Holzhauer, C.; Mehta, R.; Rubio, C.; Williams, G.; Wilson, M.; Royds, J. A.; Baird, M. A.; Braithwaite, A. W.
- Abstract
We propose that the apoptotic function of p53 has an important role in B-cell homeostasis, which is important for the prevention of B-cell lymphomas. We created a mouse model (mΔpro) that lacked residues 58–88 of the proline-rich domain of p53. mΔpro is defective for apoptosis, but is able to arrest cell-cycle progression in hematopoietic tissues. mΔpro develops late-onset B-cell lymphoma, but not the thymic T-cell tumors found in p53-null mice. Interestingly, mΔpro lymphomas comprised incorrectly differentiated B cells. B-cell irregularities were also detected in mΔpro before tumor onset, in which aged mice showed an increased population of inappropriately differentiated B cells in the bone marrow and spleen. We predict that by keeping B-cell populations in check, p53-dependent apoptosis prevents irregular B cells from eventuating in lymphomas.
- Subjects
B cells; ANTIGEN presenting cells; LYMPHOMAS; LYMPHOPROLIFERATIVE disorders; RETICULOENDOTHELIAL granulomas
- Publication
Cell Death & Differentiation, 2010, Vol 17, Issue 3, p540
- ISSN
1350-9047
- Publication type
Article
- DOI
10.1038/cdd.2009.136