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 I (RAG-I) mRNA in bone marro w cells decreases to a minimal level by the age of 10 months. Recominbant i nterleukin-7 (rIL-7) is a potent proliferative stimulus for B cell progenit ors and unpregulates RAG-I expression in Lymphocyte precursors. To investig ate the stimulatory effect of rIL-7 on the expression of RAG-I in old mice, Re compared the level of RAG-1 message in short-term bone marrow cultures of cells from mice aged I month and 18 months. We found similar levels of R AG-1 mRNA in bone marrow cells of young mice before and after 24 hours of i ncubation. No RIG-I 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-I mRNA was detected after 24 hours of incubation amid 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-7 per 10(6) old nu cleated cells yielding the maximal response. Our results indicate that desp ite the low or no RAG-I expression in bone marrow cultures of old mice, the potential to activate RAG-I in B-cell precursors is still present, and imm unoglobulin heavy chain (V(H)D(H)J(H)) rearrangement may be enhanced by rIL -7.