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 th ymic-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 an d that fewer pre-B cells express RAG protein. This combination of even ts 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 de velopment was suggested by the similar kinetics of thymic involution a nd of declining bone marrow RAG-1 gene expression during aging. Suppor t 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 marr ow pre-B cells in nude and old mice. Furthermore, in vivo CD8(+) T cel ls 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-defic ient 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 c ells. We conclude that the impaired development of B cells within the bone marrow of thymic-deprived nude and old mice can be reversed, at l east in part, by the administration of rIL-16.