Role of a two-chain IL-6 receptor system in immune and hematopoietic cell regulation

Three factors with distinct function are involved in the regulation of the B-cell response into antibody-producing cells: (1) a factor for the activation of resting B cells (BSF1/IL-4), (2) a factor for the growth of activated B cells (BCGFII/IL-5), and (3) a factor for the final maturation of B cells into antibody-producing cells (BSF2/IL-6). The cDNAs for these three molecules have been cloned, and studies with recombinant molecules demonstrated that their individual functions were not confined to the B-lineage cells; they were found to have a wide variety of biological functions. A typical example of a pleiotropic function of such interleukins is BSF2/IL-6. BSF2/IL-6 is not only a B-cell-differentiation factor, but also is a potent growth factor for myeloma cells. Moreover, BSF2/IL-6 acts as hepatocyte-stimulating factor to induce acute-phase proteins and multicolony-stimulating factor to activate hematopoietic stem cells. It appears that BSF2/IL-6 plays an essential role in the host defense mechanisms against infections, inflammation, and injury. Receptors for BSFs have not yet been molecularly cloned because of the low density of receptor molecules. Recently, the cloning of the cDNA for BSF2/IL-6 receptor has been achieved and its molecular structure and the signals transduced through it are described herein.