Abstract
To identify factors influencing the in vivo proliferate activity of bone marrow pre‐B cells, the metaphase‐blocking drug, vincristine sulfate, was injected into (a) mice depleted of B lymphocytes by treatment with anti‐mouse IgM antibodies from birth; (b) hematologically deficient WWv and SI/SId mutants, and (c) mice injected with a foreign agent, sheep red blood cells (SRBC). Subsequently, a quantitative measure of pre‐B cell proliferation was provided by examining marrow cells by immunofluorescence labeling for the absolute number of pre‐B cells, identified by the presence of cytoplasmic μ chains (cμ) without surface μ (sμ), which had been arrested in meta‐phase. In anti‐IgM‐treated mice, some changes were observed in the size of the large pre‐B cell population and in the incidence of mitotic cells after vincristine administration, but the overall production rate of pre‐B cells did not differ from that in controls given normal rabbit serum. Pre‐B cell kinetics in WW and SI/SId mice also generally resembled those in homozygous controls. In contrast, after SRBC injection, there was an increase in the rate at which large pre‐B cells entered mitosis. Thus, the proliferation of cμ+sμ‐ bone marrow pre‐B cells shows no evidence of feedback control from the mature B lymphocyte pool, as indicated by lack of stimulation of pre‐B cell production in anti‐IgM‐treated mice, and is independent of the hemopoietic defects of WW or SI/SId mutants. On the other hand, the increased bone marrow pre‐B cell proliferation after SRBC injection demonstrates that the magnitude of B cell genesis in the bone marrow can be influenced by extrinsic agents and thus may be influenced by environmental stimuli.