Maturation of B cell precursors is impaired in thymic-deprived nude and old mice.
We have previously reported that bone marrow B cell precursors from thymic-deprived nude and old mice express less recombination-activating gene-1 (RAG-1) mRNA than they do in young euthymic mice. We now report that both nude and old mice have decreased bone marrow pre-B cells and that fewer pre-B cells express RAG protein. This combination of events appears to be the basis for the lower level of bone marrow RAG mRNA in thymic-deprived mice. A link between thymic function and B cell development was suggested by the similar kinetics of thymic involution and of declining bone marrow RAG-1 gene expression during aging. Support for this hypothesis was obtained by demonstrating that injection of supernatant medium from activated CD8+ but not CD4+ young T cells from mice increases RAG mRNA, RAG protein, and the number of bone marrow pre-B cells in nude and old mice. Furthermore, in vivo CD8+ T cells also regulate bone marrow RAG gene expression. Thus, mice deficient in CD8+ T cells expressed levels of RAG-1 mRNA in their bone marrow that were only 10% of those observed in normal or CD4+ T cell-deficient mice. IL-16 was detected in the supernatant medium from activated T cell cultures, and injection of nanogram quantities of recombinant IL-16 (rIL-16) into nude or old mice increased the levels of RAG mRNA in bone marrow B cell precursors and the number of bone marrow pre-B cells. We conclude that the impaired development of B cells within the bone marrow of thymic-deprived nude and old mice can be reversed, at least in part, by the administration of rIL-16.
Szabo
P
P
Division of Geriatrics and Gerontology, Cornell University Medical College, New York 10021, USA.
Zhao
K
K
Kirman
I
I
Le Maoult
J
J
Dyall
R
R
Cruikshank
W
W
Weksler
M E
ME
D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D001854:Bone Marrow Cells / Q000201:enzymology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002474:Cell-Free System / Q000276:immunology; D004253:DNA Nucleotidylexotransferase / Q000235:genetics; D005260:Female; D016654:Genes, RAG-1 / Q000276:immunology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007275:Injections, Intravenous; D019410:Interleukin-16 / Q000008:administration & dosage; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology
D018398:Homeodomain Proteins; D019410:Interleukin-16; D012333:RNA, Messenger; C064658:RAG-1 protein; D004253:DNA Nucleotidylexotransferase