INCREASED APOPTOSIS OF BONE-MARROW PRE-B CELLS IN OLD MICE ASSOCIATEDWITH THEIR LOW NUMBER

The number of bone marrow pre-a cells is significantly lower in 18- th an in 2-month-old BALB/c mice. The percentage of apoptotic pre-a cells , freshly isolated or cultured, from 18-month-old mice was significant ly greater than from P-month-old mice. The increased percentage of apo ptotic pre-a cells from old mice was associated with a decreased level of bcl-x(L) mRNA, detected by RT-PCR, and of Bcl-x(L) protein, detect ed by intracellular staining. Consistent with an age-associated increa se in apoptosis in pre-a cells was the fact that significantly fewer p re-a cells were generated after in vitro cultures of pro-a cells from old as compared to young mice, Furthermore, fewer pre-a cells survived and fewer sig-expressing a cells were generated in cultures of pre-a cells from old as compared to young mice. In addition, there was no de tectable difference in the secretion of IL-7 by bone marrow cells from 2- or 18-month-old mice. Thus, increased apoptosis of bone marrow pre -a cells in old mice appears to contribute to their decreased number.