Precursor B Cell Receptor–Dependent B Cell Proliferation and Differentiation Does Not Require the Bone Marrow or Fetal Liver Environment

The capacity of precursor B (pre-B) I cells from fetal liver and bone marrow to proliferate and differentiate into surface immunoglobulin–positive immature B cells in vitro was analyzed. Both fetal liver– and bone marrow–derived progenitors do so in a pre-B cell receptor (pre-BCR)–dependent manner in tissue culture medium alone, without addition of other cells or cytokines. Approximately 20% of the initial pre-B I cells enter more than one division. Analyses at the single-cell level show that ∼15% divide two to five times. Coculture of pre-B I cells with stromal cells did not enhance proliferation or differentiation, whereas the presence of interleukin 7, especially in combination with stromal cells, resulted mainly in the expansion of pre-B I cells and prevented their further differentiation. Thus, the environment of fetal liver or bone marrow is not required for the pre-BCR to exert its function, which is to select and expand cells that have undergone an inframe V_H-D_HJ_H rearrangement that produces a pre-BCR–compatible μH chain. It appears unlikely that a ligand for the pre-BCR drives this pre-B cell proliferation.