Activation of the Recombination Activating Gene 1 (RAG-1) Transcript in Bone Marrow of Senescent C57BL/6 Mice by Recombinant Interleukin-7

The level of the recombination activating gene 1 (RAG-1) mRNA in bone marrow cells decreases to a minimal level by the age of 10 months. Recominbant interleukin-7 (rIL-7) is a potent proliferative stimulus for B cell progenitors and upregulates RAG-1 expression in lymphocyte precursors. To investigate the stimulatory effect of rlL-7 on the expression of RAG-1 in old mice, we compared the level of RAG-1 message in short-term bone marrow cultures of cells from mice aged 1 month and 18 months. We found similar levels of RAG-1 mRNA in bone marrow cells of young mice before and after 24 hours of incubation. No RAG-1 mRNA was detected in bone marrow cell cultures prepared from old mice after 24 hours of incubation. However, when rIL-7 was added to the culture medium, RAG-1 mRNA was detected after 24 hours of incubation and its level was similar to that measured in cells from young mice. The expression of RAG-1 was dose-dependent, with 20 ng of rIL-7per 10 6 old nucleated cells yielding the maximal response. Our results indicate that despite the low or no RAG-1 expression in bone marrow cultures of old mice, the potential to activate RAG-1 in B-cell precursors is still present, and immunoglobulin heavy chain (V H D H J H ) rearrangement may be enhanced by rIL-7.