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 α and β) 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.