Dynamics of early b lymphocyte precursor cells in mouse bone marrow: proliferation of cells containing terminal deoxynucleotidyl transferase

Abstract

Three populations of early B lymphocyte precursor cells lacking mu heavy chains have been defined in mouse bone marrow, based on immunofluorescence labeling for terminal deoxynucleotidyl transferase (TdT) and B220 glycoprotein, as detected by monoclonal antibody 14.8 (TdT+14.8- cells; TdT+14.8+ cells; TdT-14.8+ cells). We have now analyzed the frequency, size distribution, proliferation and production rates of TdT+ cells in mouse bone marrow. These formed well-defined populations of medium-sized cells, the TdT+14.8+ cells tending to be larger than TdT+14.8- cells (modal cell diameters in cytocentrifuge preparations; 10.0 microns and 9.0 microns, respectively). Some TdT+ cells (1%-2%) were normally in metaphase, the TdT being dispersed through the cytoplasm. After inducing mitotic arrest with vincristine, the incidence of TdT+ cells in metaphase increased linearly from 2 to 4 h, indicating a turnover of 5.1%/h for TdT+14.8- cells and 9.0%/h for TdT+14.8+ cells. Subtraction of turnover data for TdT+14.8+ cells from those previously obtained for 14.8+ mu- cells gave values for the population of TdT-14.8+ cells. The calculated daily turnover of cells in the three compartments increased progressively (TdT+14.8-, 2.5 x 10(6) cells; TdT+14.8+, 5.0 x 10(6) cells; TdT-14.8+, 36.0 x 10(6) cells), accompanied by a shortening of the average apparent cell cycle time (TdT+14.8-, 20 h; TdT+14.8+, 11 h; TdT-14.8+, 8 h). The results demonstrate a progressive expansion of cell production at three putatively successive stages of early B lymphocyte development before the expression of mu chains. The findings contribute to a kinetic model of primary B cell genesis in mouse bone marrow.