GP130 TRANSDUCING RECEPTOR CROSS-LINKING IS SUFFICIENT TO INDUCE INTERLEUKIN-6 TYPE RESPONSES

gp130 transducing receptor is involved in the formation of high affini ty receptors for the cytokines of the interleukin-6 (IL-6) family. Rec ruitment of gp130 by IL-6 associated to its receptor leads to the dime rization of the transducing component, In the present study we did cha racterize the B-S12 monoclonal antibody raised against gp130 and able to elicit IL-6 type biological activities. B-S12 antibody triggered st rongly the proliferation of TF1 and XG1 hematopoietic cell lines and w as able to increase the synthesis of acute phase proteins in HepG2 hep atoma cell line. B-S12 also behaved as a synergistic factor with granu locyte-macrophage colony-stimulating factor for both proliferation and differentiation of CD34-positive hematopoietic cell progenitors. By u sing a symmetric enzyme-linked immunosorbent assay, allowing the detec tion of dimeric forms of soluble gp130, we found that addition of B-S1 2 to gp130 led to its dimerization. Analysis of the tyrosine phosphory lation events in gp130 and Jak kinase family members revealed that B-S 12 quickly induced the phosphorylation of gp130 in a neural derived ce ll line, and that Jak1 and Jak2 were also recruited. In conclusion, we show that gp130 cross-linking with the B-S12 monoclonal antibody was sufficient to generate functional IL-6 type responses in hematopoietic , neural, and hepatic cells.