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Maturation of B Cell Precursors Is Impaired in Thymic-Deprived Nude and Old Mice¹

Paul Szabo^*, Kesheng Zhao^*, Irena Kirman^*, Joel Le Maoult^*, Rubendra Dyall, William Cruikshank and Marc E. Weksler^2,*

^* Division of Geriatrics and Gerontology, Cornell University Medical College, New York, NY 10021; Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and The Pulmonary Center, Boston University School of Medicine, Boston, MA 02118

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.

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