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 rIL-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-7 per 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 rIL7.
Ben-Yehuda
A
A
Division of Medicine, Geriatric Unit, Hadassah University Hospital, Jerusalem, Israel.
Wirtheim
E
E
Abdul-Hai
A
A
Or
R
R
Slavin
S
S
Babaey
S
S
Friedman
G
G
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D016654:Genes, RAG-1 / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D015851:Interleukin-7 / Q000008:administration & dosage / Q000494:pharmacology*; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D014158:Transcription, Genetic / Q000235:genetics*; D015854:Up-Regulation
D015851:Interleukin-7; D012333:RNA, Messenger; D011994:Recombinant Proteins