Dimerization and activation of the common transducing chain (gp130) of the cytokines of the IL-6 family by mAb.
The objective of our research was to study the mechanisms of activation of mAb against the gp130 transducer chain common to the IL-6 cytokine family. It has been found that among the 56 anti-gp130 available worldwide, none was able to activate the growth of IL-6-dependent myeloma cell lines. When certain of them were associated in pairs they allowed the cells to grow; alone, they were inhibitory. The same activation was also obtained by cross-linking certain anti-gp130 mAb on the cell membrane with a goat anti-mouse Ig antiserum. A bispecific mAb was prepared by the somatic fusion of two hybridomas secreting two mAb whose association was able to activate gp130 signaling; the bispecific mAb was inactive. The activating mAb were able to support long-term proliferation of the IL-6-dependent myeloma cell lines, which indicates that they are potential valuable growth factors of tumor cells and hematopoietic stem cells. When they were injected into SCID mice, they allowed human IL-6-dependent myeloma cell lines to grow, develop tumors and metastasize. By studying the functional epitopes of the cell membrane gp130 receptors, it was shown that the activating mAb induced gp130 dimerization and STAT3 activation, as did IL-6.
Autissier
P
P
INSERM U475, Montpellier, France.
De Vos
J
J
Liautard
J
J
Tupitsyn
N
N
Jacquet
C
C
Chavdia
N
N
Klein
B
B
Brochier
J
J
Gaillard
J P
JP
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division / Q000276:immunology; D050822:Cytokine Receptor gp130; D019281:Dimerization; D006041:Goats; D006133:Growth Substances / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D015398:Signal Transduction / Q000276:immunology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006133:Growth Substances; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D050822:Cytokine Receptor gp130