Increased apoptosis of bone marrow pre-B cells in old mice associated with their low number.

The number of bone marrow pre-B cells is significantly lower in 18- than in 2-month-old BALB/c mice. The percentage of apoptotic pre-B cells, freshly isolated or cultured, from 18-month-old mice was significantly greater than from 2-month-old mice. The increased percentage of apoptotic pre-B cells from old mice was associated with a decreased level of bcl-xL mRNA, detected by RT-PCR, and of Bcl-xL protein, detected by intracellular staining. Consistent with an age-associated increase in apoptosis in pre-B cells was the fact that significantly fewer pre-B cells were generated after in vitro cultures of pro-B cells from old as compared to young mice. Furthermore, fewer pre-B cells survived and fewer sIg-expressing B cells were generated in cultures of pre-B cells from old as compared to young mice. In addition, there was no detectable 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-B cells in old mice appears to contribute to their decreased number.