Regulation and localization of lymphocyte production in the bone marrow.

The homeostatic mechanisms which control B lymphocyte renewal in the bone marrow are unknown. Mouse bone marrow produces many small lymphocytes which develop surface IgM and other B lymphocyte properties. Putative precursors show cytoplasmic mu chains but earlier progenitors have been characterized. Some marrow small lymphocytes are long-lived recirculating B and T cells. [3H]Thymidine and IgM labelling in femoral marrow sections suggest that recirculating lymphocytes migrate mainly through the marrow periphery while indigenous lymphocytes may be formed peripherally and migrate centrally as they mature. Thus, the localization of lymphocytes appears to be non-random. The effects of possible regulatory factors on bone marrow small lymphocytes production have been examined by [3H]thymidine labelling and radioautography. Administration of anti-IgM antibodies in vivo eliminates all B lymphocytes but the marrow lymphocyte production rate remains unchanged. After sublethal X-irradiation the marrow shows an over-shoot B lymphocyte production, while the lymphocyte numbers in shielded marrow remain stable. In neonatally thymectomized or congenitally athymic mice marrow lymphocyte production is unaffected. Studies in germ-free and antigen-stimulated mice reveal a basal level of marrow lymphocyte production, normally stimulated non-specifically by environmental factors. Thus, marrow lymphocyte production appears to be basically independent of feedback control from the peripheral B lymphocyte pool or of specific humoral factors, but fluctuates widely after perturbation or when amplified by exogenous stimuli. These findings suggest the importance of microenvironmental factors, as yet undefined, in the regulation of bone marrow lymphocytes.