In vivo regulation of B lymphocyte production in the bone marrow: effects and mechanism of action of exogenous stimuli on pre-B cell proliferation and lymphocyte turnover.

The present studies demonstrate that a single administration of an extrinsic agent (SRBC) can stimulate increased production of B lymphocytes in mouse bone marrow as revealed by 2 in vivo assays which quantitate pre-B cell proliferation and small lymphocyte renewal, respectively. The mechanisms mediating this stimulatory effect are sensitive to silica in vivo and require the presence of the spleen. Early events are both silica-sensitive and spleen-dependent, while a subsequent stage appears still to be spleen-dependent but not silica-sensitive. Sustained exogenous stimulation by multiple SRBC injections for 4 wk in young mice produces an expanded population size and increased production of pre-B cells and B lymphocytes in the bone marrow, apparently an elevated kinetic steady state of B lymphocyte production. (Formula: see text). As depicted schematically in Figure 1, the results suggest that the magnitude of bone marrow B lymphocyte production in vivo may reflect a basal level, putatively regulated by microenvironmental and other endogenous factors, which is amplified by exogenous environmental stimuli mediated by the action of macrophages located in the spleen. Further questions about such an environmental amplification (Fig. 1) concern the nature of later events in the spleen, the identity of putative stimulatory factors or cells circulating from the spleen to the bone marrow, the receptive target cell stages in the bone marrow and the consequences of this process with respect to the size and diversity of B lymphocyte clones and of primary humoral immune responses in vivo.