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 (mDpro) that lacked residues 58-88 of the proline-rich domain of p53. mDpro is defective for apoptosis, but is able to arrest cell-cycle progression in hematopoietic tissues. mDpro develops late-onset B-cell lymphoma, but not the thymic T-cell tumors found in p53-null mice. Interestingly, mDpro lymphomas comprised incorrectly differentiated B cells. B-cell irregularities were also detected in mDpro 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.

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