Cytokine regulation of early lymphohematopoietic development

A two-step methylcellulose culture provided a method to study the differentiation of murine lymphohematopoietic progenitors. In the presence of two cytokines, one from a group consisting of Steel factor (SF) and flt3/flk2 ligand (FL) and the other from a group consisting of interleukin 6 (IL-6), G-CSF, IL-11 and IL-12, murine lymphohematopoietic progenitors proliferated and generated not only myeloid lineage cells but also committed B cell progenitors. Although somewhat less effectively than SF and FL, IL-4 also synergized with IL-6 or IL-11 in support of B lymphopoiesis. This early process of B lymphopoiesis appears to proceed through three stages: lymphohematopoietic proliferative stage, commitment stage and early B lymphoid proliferative stage. Surprisingly, IL-3 could neither replace nor act synergistically with SF, IL-4 or FL in maintaining the B lymphoid potential of the cells in the primary culture, although IL-3 was very effective in support of multilineage myeloid colony formation. In addition, when added to permissive cytokine combinations, IL-3 inhibited development of the B cell lineage. After screening available lymphohematopoietic cytokines, it was found that IL-1 (both alpha and beta) also has similar inhibitory effects on early B lymphopoiesis. Studies using in vivo transfer of primary colonies suggested that cytokine regulation of commitment to T cell lineage may also be similar to that of B cell lineage.