Modulation of early B lymphopoiesis by interleukin-3

We recently reported that interleukin-3 (IL-3) inhibits B lymphoid lineage expression in methylcellulose culture in a dose-dependent manner. We subsequently used flow cytometric analysis of individual colonies in timed exposure to IL-3 to define more precisely the negative regulatory role of IL-3 in early B lymphopoiesis. When lymphohematopoietic progenitors isolated from 5-fluorouracil (5-FU)-treated mice were cultured in the presence of Steel factor (SF), IL-11, IL-7, and erythropoietin (Epo), B lymphopoiesis appeared to proceed through three stages: lymphohematopoietic proliferation, commitment, and early B lymphoid proliferation. When IL-3 was added to the culture for a 48-hour interval from days 4 to 6 of culture, IL-3 slightly enhanced the formation of pre-B cell colonies. These data appeared to contradict our previous observations that continued exposure to IL-3 from days 0 to 4 or longer severely inhibits B lymphoid potential of the cultured cells. A more frequently timed kinetic observation revealed that in the presence of IL-3 the peak of lymphohematopoietic progenitors was 48 hours earlier but less than one-tenth the number of lymphohematopoietic progenitors in cultures without IL-3. When added to cultures for 48 hours beyond day 6 of culture, IL-3 abrogated the B cell potential of the cultured cells. However, IL-3 failed to negatively modulate B lymphoid progenitors when added on day 14 of culture or later. These observations indicate that IL-3 is a potent negative modulator of the early B lymphopoiesis. IL-3 appears to hasten but suppress the proliferation and commitment of lymphohematopoietic progenitors to B cell lineage. It may also inhibit the proliferation of the progenitors immediately after commitment to B cell lineage.