Stepwise progression of B lineage differentiation supported by interleukin 7 and other stromal cell molecules.

Growth of early B precursor cells was investigated in vitro by using rIL-7 and IL-7-defective stromal cell line PA6 as separate growth signals. B cell development proceeds through three sequential stages different from the growth signal requirement. The cells in the first stage require PA6 alone for the proliferation, and differentiate into the second stage, which requires both PA6 and IL-7 for its growth. When IL-7 is available for the cells in the second stage, they proliferate extensively on the PA6 layer, and some acquire the ability to proliferate in response to IL-7 alone. This sequential change of growth signal requirement, however, does not proceed autonomously along the time schedule. The possibility that it is primarily directed by the result of Ig gene rearrangement is considered. This mode of growth control may explain why only functional B cells are selected in the error-prone process of Ig gene rearrangement during B lineage differentiation.