Many B cell precursors die during differentiation in mouse bone marrow. To examine mechanisms involved in this process, B lineage ceUs and their tissue organisation were analysed in transgenic mice overexpressing the apoptosis inhibitor, 8cl-2. lmmunofluorescence labeling and mitotic arrest were used to quantitate the nun: ber and proliferative activity of~-pro-B cells (TdT+ S220-; TdT+ B220+; TdT-B220+), pre-B cells (c~+) and B cells (SJl+). In bone marrow, mature B cells (lgM+ lgO+) and immature B ceUs (lgM+ lgO-/low) were increased 16-20 fold and 3-6 fold, respectively. Pre-B cells and late pro-B cells were increased in number and production rate, but earlier pro-B cells expressing TdT were unaffected. In spleen, both mature and immature 8 cells were greatly increased, but cells of precursor phenotype were few and TdT+ ceUs were absent. The in vivo localisation of B ceUs was examined by light and electron microscope radioautography after Lv. injection of 1251-labeled antibodies. 8220+ ceUs were increased throughout the bone marrow, many located within dilated venous sinusoids particularly in subosteal regions. Many intravascular and perisinusoidal cells were IgOhigh lymphocytes. In contrast, most IgM+ cells and Igolow cells were extravascular, concentrated around the central venous sinus. Plasma ceUs with distended endoplasmic reticulum were numerous. Thus, bcl-2 transgenic mice show increased levels of proliferating precursor B cells and immature B lymphocytes within bone marrow parenchyma, as weil as mature B lymphocytes entering fram the blood stream. These findings provide evidence that high levels of Bcl-2 can inhibit the cell death normally occurring during B Iymphopoiesis in bone marrow, thereby expanding the mature B cell pool.