p53-mediated apoptosis prevents the accumulation of progenitor B cells and B-cell tumors

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 (m Delta pro) that lacked residues 58-88 of the proline-rich domain of p53. m Delta pro is defective for apoptosis, but is able to arrest cell-cycle progression in hematopoietic tissues. m Delta pro develops late-onset B-cell lymphoma, but not the thymic T-cell tumors found in p53-null mice. Interestingly, m Delta pro lymphomas comprised incorrectly differentiated B cells. B-cell irregularities were also detected in m Delta pro 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. Cell Death and Differentiation (2010) 17, 540-550; doi: 10.1038/cdd.2009.136; published online 25 September 2009